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| Publications of Staci D. Bilbo :chronological alphabetical combined listing:
%% Journal Articles
@article{fds374234,
Author = {Bordt, EA and Moya, HA and Jo, YC and Ravichandran, CT and Bankowski,
IM and Ceasrine, AM and McDougle, CJ and Carlezon, WA and Bilbo,
SD},
Title = {Gonadal hormones impart male-biased behavioral
vulnerabilities to immune activation via microglial
mitochondrial function.},
Journal = {Brain, behavior, and immunity},
Volume = {115},
Pages = {680-695},
Year = {2024},
Month = {January},
url = {http://dx.doi.org/10.1016/j.bbi.2023.11.010},
Abstract = {There is a strong male bias in the prevalence of many
neurodevelopmental disorders such as autism spectrum
disorder. However, the mechanisms underlying this sex bias
remain elusive. Infection during the perinatal period is
associated with an increased risk of neurodevelopmental
disorder development. Here, we used a mouse model of
early-life immune activation that reliably induces deficits
in social behaviors only in males. We demonstrate that
male-biased alterations in social behavior are dependent
upon microglial immune signaling and are coupled to
alterations in mitochondrial morphology, gene expression,
and function specifically within microglia, the innate
immune cells of the brain. Additionally, we show that this
behavioral and microglial mitochondrial vulnerability to
early-life immune activation is programmed by the
male-typical perinatal gonadal hormone surge. These findings
demonstrate that social behavior in males over the lifespan
are regulated by microglia-specific mechanisms that are
shaped by events that occur in early development.},
Doi = {10.1016/j.bbi.2023.11.010},
Key = {fds374234}
}
@article{fds370885,
Author = {Smith, CJ and Rendina, DN and Kingsbury, MA and Malacon, KE and Nguyen,
DM and Tran, JJ and Devlin, BA and Raju, RM and Clark, MJ and Burgett, L and Zhang, JH and Cetinbas, M and Sadreyev, RI and Chen, K and Iyer, MS and Bilbo, SD},
Title = {Microbial modulation via cross-fostering prevents the
effects of pervasive environmental stressors on microglia
and social behavior, but not the dopamine
system.},
Journal = {Molecular psychiatry},
Volume = {28},
Number = {6},
Pages = {2549-2562},
Year = {2023},
Month = {June},
url = {http://dx.doi.org/10.1038/s41380-023-02108-w},
Abstract = {Environmental toxicant exposure, including air pollution, is
increasing worldwide. However, toxicant exposures are not
equitably distributed. Rather, low-income and minority
communities bear the greatest burden, along with higher
levels of psychosocial stress. Both air pollution and
maternal stress during pregnancy have been linked to
neurodevelopmental disorders such as autism, but biological
mechanisms and targets for therapeutic intervention remain
poorly understood. We demonstrate that combined prenatal
exposure to air pollution (diesel exhaust particles, DEP)
and maternal stress (MS) in mice induces social behavior
deficits only in male offspring, in line with the male bias
in autism. These behavioral deficits are accompanied by
changes in microglial morphology and gene expression as well
as decreased dopamine receptor expression and dopaminergic
fiber input in the nucleus accumbens (NAc). Importantly, the
gut-brain axis has been implicated in ASD, and both
microglia and the dopamine system are sensitive to the
composition of the gut microbiome. In line with this, we
find that the composition of the gut microbiome and the
structure of the intestinal epithelium are significantly
shifted in DEP/MS-exposed males. Excitingly, both the
DEP/MS-induced social deficits and microglial alterations in
males are prevented by shifting the gut microbiome at birth
via a cross-fostering procedure. However, while social
deficits in DEP/MS males can be reversed by chemogenetic
activation of dopamine neurons in the ventral tegmental
area, modulation of the gut microbiome does not impact
dopamine endpoints. These findings demonstrate male-specific
changes in the gut-brain axis following DEP/MS and suggest
that the gut microbiome is an important modulator of both
social behavior and microglia.},
Doi = {10.1038/s41380-023-02108-w},
Key = {fds370885}
}
@article{fds369662,
Author = {Bilbo, S and Smith, C and Rendina, D and Kingsbury, M and Malacon, K and Nguyen, D and Tran, J and Devlin, B and Raju, R and Clark, M and Burgett,
L and Zhang, J and Cetinbas, M and Sadreyev, R and Chen, K and Iyer,
M},
Title = {Microbial modulation prevents the effects of pervasive
environmental stressors on microglia and social behavior,
but not the dopamine system.},
Journal = {Res Sq},
Year = {2023},
Month = {February},
url = {http://dx.doi.org/10.21203/rs.3.rs-2548369/v1},
Abstract = {Environmental toxicant exposure, including air pollution, is
increasing worldwide. However, toxicant exposures are not
equitably distributed. Rather, low-income and minority
communities bear the greatest burden, along with higher
levels of psychosocial stress. Both air pollution and
maternal stress during pregnancy have been linked to
neurodevelopmental disorders such as autism, but biological
mechanisms and targets for therapeutic intervention remain
poorly understood. We demonstrate that combined prenatal
exposure to air pollution (diesel exhaust particles, DEP)
and maternal stress (MS) in mice induces social behavior
deficits only in male offspring, in line with the male bias
in autism. These behavioral deficits are accompanied by
changes in microglial morphology and gene expression as well
as decreased dopamine receptor expression and dopaminergic
fiber input in the nucleus accumbens (NAc). Importantly, the
gut-brain axis has been implicated in ASD, and both
microglia and the dopamine system are sensitive to the
composition of the gut microbiome. In line with this, we
find that the composition of the gut microbiome and the
structure of the intestinal epithelium are significantly
shifted in DEP/MS-exposed males. Excitingly, both the
DEP/MS-induced social deficits and microglial alterations in
males are prevented by shifting the gut microbiome at birth
via a cross-fostering procedure. However, while social
deficits in DEP/MS males can be reversed by chemogenetic
activation of dopamine neurons in the ventral tegmental
area, modulation of the gut microbiome does not impact
dopamine endpoints. These findings demonstrate male-specific
changes in the gut-brain axis following DEP/MS and suggest
that the gut microbiome is an important modulator of both
social behavior and microglia.},
Doi = {10.21203/rs.3.rs-2548369/v1},
Key = {fds369662}
}
@article{fds366200,
Author = {Ceasrine, AM and Green, LA and Bilbo, SD},
Title = {Protocol to measure endotoxin from opaque tissues in mice
using an optimized kinetic limulus amebocyte lysate
assay.},
Journal = {STAR protocols},
Volume = {3},
Number = {4},
Pages = {101669},
Year = {2022},
Month = {December},
url = {http://dx.doi.org/10.1016/j.xpro.2022.101669},
Abstract = {Endotoxin accumulation has been widely noted in several
pathologies ranging from metabolic dysregulation to
bacterial infection. Using limulus amebocyte lysate (LAL)
assays to detect endotoxin load has been the only reliable
way to assess endotoxin accumulation, but assays optimized
for detection in opaque tissues are still lacking. We
optimized a sensitive Kinetic LAL assay for endotoxin
detection from murine tissues. In this protocol, we describe
tissue collection and homogenization, followed by the
procedure to run the assay and data analysis. For complete
details on the use and execution of this protocol, please
refer to Ceasrine et al. (2022).},
Doi = {10.1016/j.xpro.2022.101669},
Key = {fds366200}
}
@article{fds368398,
Author = {Ceasrine, AM and Devlin, BA and Bolton, JL and Green, LA and Jo, YC and Huynh, C and Patrick, B and Washington, K and Sanchez, CL and Joo, F and Campos-Salazar, AB and Lockshin, ER and Kuhn, C and Murphy, SK and Simmons, LA and Bilbo, SD},
Title = {Maternal diet disrupts the placenta-brain axis in a
sex-specific manner.},
Journal = {Nat Metab},
Volume = {4},
Number = {12},
Pages = {1732-1745},
Year = {2022},
Month = {December},
url = {http://dx.doi.org/10.1038/s42255-022-00693-8},
Abstract = {High maternal weight is associated with detrimental outcomes
in offspring, including increased susceptibility to
neurological disorders such as anxiety, depression and
communicative disorders. Despite widespread acknowledgement
of sex biases in the development of these disorders, few
studies have investigated potential sex-biased mechanisms
underlying disorder susceptibility. Here, we show that a
maternal high-fat diet causes endotoxin accumulation in
fetal tissue, and subsequent perinatal inflammation
contributes to sex-specific behavioural outcomes in
offspring. In male offspring exposed to a maternal high-fat
diet, increased macrophage Toll-like receptor 4 signalling
results in excess microglial phagocytosis of serotonin
(5-HT) neurons in the developing dorsal raphe nucleus,
decreasing 5-HT bioavailability in the fetal and adult
brains. Bulk sequencing from a large cohort of matched
first-trimester human samples reveals sex-specific
transcriptome-wide changes in placental and brain tissue in
response to maternal triglyceride accumulation (a proxy for
dietary fat content). Further, fetal brain 5-HT levels
decrease as placental triglycerides increase in male mice
and male human samples. These findings uncover a
microglia-dependent mechanism through which maternal diet
can impact offspring susceptibility for neuropsychiatric
disorder development in a sex-specific manner.},
Doi = {10.1038/s42255-022-00693-8},
Key = {fds368398}
}
@article{fds368470,
Author = {Hermann, AL and Fell, GL and Kemény, LV and Fung, CY and Held, KD and Biggs, PJ and Rivera, PD and Bilbo, SD and Igras, V and Willers, H and Kung, J and Gheorghiu, L and Hideghéty, K and Mao, J and Woolf, CJ and Fisher, DE},
Title = {β-Endorphin mediates radiation therapy fatigue.},
Journal = {Science advances},
Volume = {8},
Number = {50},
Pages = {eabn6025},
Year = {2022},
Month = {December},
url = {http://dx.doi.org/10.1126/sciadv.abn6025},
Abstract = {Fatigue is a common adverse effect of external beam
radiation therapy in cancer patients. Mechanisms causing
radiation fatigue remain unclear, although linkage to skin
irradiation has been suggested. β-Endorphin, an endogenous
opioid, is synthesized in skin following genotoxic
ultraviolet irradiation and acts systemically, producing
addiction. Exogenous opiates with the same receptor activity
as β-endorphin can cause fatigue. Using rodent models of
radiation therapy, exposing tails and sparing vital organs,
we tested whether skin-derived β-endorphin contributes to
radiation-induced fatigue. Over a 6-week radiation regimen,
plasma β-endorphin increased in rats, paralleled by opiate
phenotypes (elevated pain thresholds, Straub tail) and
fatigue-like behavior, which was reversed in animals treated
by the opiate antagonist naloxone. Mechanistically, all
these phenotypes were blocked by opiate antagonist treatment
and were undetected in either β-endorphin knockout mice or
mice lacking keratinocyte p53 expression. These findings
implicate skin-derived β-endorphin in systemic effects of
radiation therapy. Opioid antagonism may warrant testing in
humans as treatment or prevention of radiation-induced
fatigue.},
Doi = {10.1126/sciadv.abn6025},
Key = {fds368470}
}
@article{fds367609,
Author = {Paolicelli, RC and Sierra, A and Stevens, B and Tremblay, M-E and Aguzzi, A and Ajami, B and Amit, I and Audinat, E and Bechmann, I and Bennett, M and Bennett, F and Bessis, A and Biber, K and Bilbo, S and Blurton-Jones, M and Boddeke, E and Brites, D and Brône, B and Brown,
GC and Butovsky, O and Carson, MJ and Castellano, B and Colonna, M and Cowley, SA and Cunningham, C and Davalos, D and De Jager and PL and de
Strooper, B and Denes, A and Eggen, BJL and Eyo, U and Galea, E and Garel,
S and Ginhoux, F and Glass, CK and Gokce, O and Gomez-Nicola, D and González, B and Gordon, S and Graeber, MB and Greenhalgh, AD and Gressens, P and Greter, M and Gutmann, DH and Haass, C and Heneka, MT and Heppner, FL and Hong, S and Hume, DA and Jung, S and Kettenmann, H and Kipnis, J and Koyama, R and Lemke, G and Lynch, M and Majewska, A and Malcangio, M and Malm, T and Mancuso, R and Masuda, T and Matteoli, M and McColl, BW and Miron, VE and Molofsky, AV and Monje, M and Mracsko, E and Nadjar, A and Neher, JJ and Neniskyte, U and Neumann, H and Noda, M and Peng, B and Peri, F and Perry, VH and Popovich, PG and Pridans, C and Priller, J and Prinz, M and Ragozzino, D and Ransohoff, RM and Salter,
MW and Schaefer, A and Schafer, DP and Schwartz, M and Simons, M and Smith,
CJ and Streit, WJ and Tay, TL and Tsai, L-H and Verkhratsky, A and von
Bernhardi, R and Wake, H and Wittamer, V and Wolf, SA and Wu, L-J and Wyss-Coray, T},
Title = {Microglia states and nomenclature: A field at its
crossroads.},
Journal = {Neuron},
Volume = {110},
Number = {21},
Pages = {3458-3483},
Year = {2022},
Month = {November},
url = {http://dx.doi.org/10.1016/j.neuron.2022.10.020},
Abstract = {Microglial research has advanced considerably in recent
decades yet has been constrained by a rolling series of
dichotomies such as "resting versus activated" and "M1
versus M2." This dualistic classification of good or bad
microglia is inconsistent with the wide repertoire of
microglial states and functions in development, plasticity,
aging, and diseases that were elucidated in recent years.
New designations continuously arising in an attempt to
describe the different microglial states, notably defined
using transcriptomics and proteomics, may easily lead to a
misleading, although unintentional, coupling of categories
and functions. To address these issues, we assembled a group
of multidisciplinary experts to discuss our current
understanding of microglial states as a dynamic concept and
the importance of addressing microglial function. Here, we
provide a conceptual framework and recommendations on the
use of microglial nomenclature for researchers, reviewers,
and editors, which will serve as the foundations for a
future white paper.},
Doi = {10.1016/j.neuron.2022.10.020},
Key = {fds367609}
}
@article{fds364170,
Author = {Smith, CJ and Lintz, T and Clark, MJ and Malacon, KE and Abiad, A and Constantino, NJ and Kim, VJ and Jo, YC and Alonso-Caraballo, Y and Bilbo, SD and Chartoff, EH},
Title = {Prenatal opioid exposure inhibits microglial sculpting of
the dopamine system selectively in adolescent male
offspring.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {47},
Number = {10},
Pages = {1755-1763},
Year = {2022},
Month = {September},
url = {http://dx.doi.org/10.1038/s41386-022-01376-4},
Abstract = {The current opioid epidemic has dramatically increased the
number of children who are prenatally exposed to opioids,
including oxycodone. A number of social and cognitive
abnormalities have been documented in these children as they
reach young adulthood. However, little is known about the
mechanisms underlying developmental effects of prenatal
opioid exposure. Microglia, the resident immune cells of the
brain, respond to acute opioid exposure in adulthood.
Moreover, microglia are known to sculpt neural circuits
during typical development. Indeed, we recently found that
microglial phagocytosis of dopamine D1 receptors (D1R) in
the nucleus accumbens (NAc) is required for the natural
developmental decline in NAc-D1R that occurs between
adolescence and adulthood in rats. This microglial pruning
occurs only in males, and is required for the normal
developmental trajectory of social play behavior. However,
virtually nothing is known as to whether this developmental
program is altered by prenatal exposure to opioids. Here, we
show in rats that maternal oxycodone self-administration
during pregnancy leads to reduced adolescent microglial
phagocytosis of D1R and subsequently higher D1R density
within the NAc in adult male, but not female, offspring.
Finally, we show prenatal and adult behavioral deficits in
opioid-exposed offspring, including impaired extinction of
oxycodone-conditioned place preference in males. This work
demonstrates for the first time that microglia play a key
role in translating prenatal opioid exposure to changes in
neural systems and behavior.},
Doi = {10.1038/s41386-022-01376-4},
Key = {fds364170}
}
@article{fds365154,
Author = {Block, CL and Eroglu, O and Mague, SD and Smith, CJ and Ceasrine, AM and Sriworarat, C and Blount, C and Beben, KA and Malacon, KE and Ndubuizu,
N and Talbot, A and Gallagher, NM and Chan Jo and Y and Nyangacha, T and Carlson, DE and Dzirasa, K and Eroglu, C and Bilbo,
SD},
Title = {Prenatal environmental stressors impair postnatal microglia
function and adult behavior in males.},
Journal = {Cell Rep},
Volume = {40},
Number = {5},
Pages = {111161},
Year = {2022},
Month = {August},
url = {http://dx.doi.org/10.1016/j.celrep.2022.111161},
Abstract = {Gestational exposure to environmental toxins and
socioeconomic stressors is epidemiologically linked to
neurodevelopmental disorders with strong male bias, such as
autism. We model these prenatal risk factors in mice by
co-exposing pregnant dams to an environmental pollutant and
limited-resource stress, which robustly activates the
maternal immune system. Only male offspring display
long-lasting behavioral abnormalities and alterations in the
activity of brain networks encoding social interactions.
Cellularly, prenatal stressors diminish microglial function
within the anterior cingulate cortex, a central node of the
social coding network, in males during early postnatal
development. Precise inhibition of microglial phagocytosis
within the anterior cingulate cortex (ACC) of wild-type (WT)
mice during the same critical period mimics the impact of
prenatal stressors on a male-specific behavior, indicating
that environmental stressors alter neural circuit formation
in males via impairing microglia function during
development.},
Doi = {10.1016/j.celrep.2022.111161},
Key = {fds365154}
}
@article{fds361813,
Author = {Ceasrine, AM and Bilbo, SD},
Title = {Dietary fat: a potent microglial influencer.},
Journal = {Trends in endocrinology and metabolism: TEM},
Volume = {33},
Number = {3},
Pages = {196-205},
Year = {2022},
Month = {March},
url = {http://dx.doi.org/10.1016/j.tem.2021.12.005},
Abstract = {Poor nutrition, lack of exercise, and genetic predisposition
all contribute to the growing epidemic of obesity.
Overweight/obesity create an environment of chronic
inflammation that leads to negative physiological and
neurological outcomes, such as diabetes, cardiovascular
disease, and anxiety/depression. While the whole body
contributes to metabolic homeostasis, the neuroimmune system
has recently emerged as a key regulator of metabolism.
Microglia, the resident immune cells of the brain, respond
both directly and indirectly to dietary fat, and the
environment in which microglia develop contributes to their
responsiveness later in life. Thus, high maternal weight
during pregnancy may have consequences for microglial
function in offspring. Here, we discuss the most recent
findings on microglia signaling in overweight/obesity with a
focus on perinatal programming.},
Doi = {10.1016/j.tem.2021.12.005},
Key = {fds361813}
}
@article{fds359903,
Author = {Petrozziello, T and Bordt, EA and Mills, AN and Kim, SE and Sapp, E and Devlin, BA and Obeng-Marnu, AA and Farhan, SMK and Amaral, AC and Dujardin, S and Dooley, PM and Henstridge, C and Oakley, DH and Neueder,
A and Hyman, BT and Spires-Jones, TL and Bilbo, SD and Vakili, K and Cudkowicz, ME and Berry, JD and DiFiglia, M and Silva, MC and Haggarty,
SJ and Sadri-Vakili, G},
Title = {Targeting Tau Mitigates Mitochondrial Fragmentation and
Oxidative Stress in Amyotrophic Lateral Sclerosis.},
Journal = {Molecular neurobiology},
Volume = {59},
Number = {1},
Pages = {683-702},
Year = {2022},
Month = {January},
url = {http://dx.doi.org/10.1007/s12035-021-02557-w},
Abstract = {Understanding the mechanisms underlying amyotrophic lateral
sclerosis (ALS) is crucial for the development of new
therapies. Previous studies have demonstrated that
mitochondrial dysfunction is a key pathogenetic event in
ALS. Interestingly, studies in Alzheimer's disease (AD)
post-mortem brain and animal models link alterations in
mitochondrial function to interactions between
hyperphosphorylated tau and dynamin-related protein 1
(DRP1), the GTPase involved in mitochondrial fission. Recent
evidence suggest that tau may be involved in ALS
pathogenesis, therefore, we sought to determine whether
hyperphosphorylated tau may lead to mitochondrial
fragmentation and dysfunction in ALS and whether reducing
tau may provide a novel therapeutic approach. Our findings
demonstrated that pTau-S396 is mis-localized to synapses in
post-mortem motor cortex (mCTX) across ALS subtypes.
Additionally, the treatment with ALS synaptoneurosomes
(SNs), enriched in pTau-S396, increased oxidative stress,
induced mitochondrial fragmentation, and altered
mitochondrial connectivity without affecting cell survival
in vitro. Furthermore, pTau-S396 interacted with DRP1, and
similar to pTau-S396, DRP1 accumulated in SNs across ALS
subtypes, suggesting increases in mitochondrial
fragmentation in ALS. As previously reported, electron
microscopy revealed a significant decrease in mitochondria
density and length in ALS mCTX. Lastly, reducing tau levels
with QC-01-175, a selective tau degrader, prevented ALS
SNs-induced mitochondrial fragmentation and oxidative stress
in vitro. Collectively, our findings suggest that increases
in pTau-S396 may lead to mitochondrial fragmentation and
oxidative stress in ALS and decreasing tau may provide a
novel strategy to mitigate mitochondrial dysfunction in ALS.
pTau-S396 mis-localizes to synapses in ALS. ALS
synaptoneurosomes (SNs), enriched in pTau-S396, increase
oxidative stress and induce mitochondrial fragmentation in
vitro. pTau-S396 interacts with the pro-fission GTPase DRP1
in ALS. Reducing tau with a selective degrader, QC-01-175,
mitigates ALS SNs-induced mitochondrial fragmentation and
increases in oxidative stress in vitro.},
Doi = {10.1007/s12035-021-02557-w},
Key = {fds359903}
}
@article{fds359042,
Author = {Dziabis, JE and Bilbo, SD},
Title = {Microglia and Sensitive Periods in Brain
Development.},
Journal = {Current topics in behavioral neurosciences},
Volume = {53},
Pages = {55-78},
Year = {2022},
Month = {January},
url = {http://dx.doi.org/10.1007/7854_2021_242},
Abstract = {From embryonic neuronal migration to adolescent circuit
refinement, the immune system plays an essential role
throughout central nervous system (CNS) development. Immune
signaling molecules serve as a common language between the
immune system and CNS, allowing them to work together to
modulate brain function both in health and disease. As the
resident CNS macrophage, microglia comprise the majority of
immune cells in the brain. Much like their peripheral
counterparts, microglia survey their environment for
pathology, clean up debris, and propagate inflammatory
responses when necessary. Beyond this, recent studies have
highlighted that microglia perform a number of complex tasks
during neural development, from directing neuronal and
axonal positioning to pruning synapses, receptors, and even
whole cells. In this chapter, we discuss this literature
within the framework that immune activation during discrete
windows of neural development can profoundly impact brain
function long-term, and thus the risk of neurodevelopmental
and neuropsychiatric disorders. In this chapter, we review
three sensitive developmental periods - embryonic wiring,
early postnatal synaptic pruning, and adolescent circuit
refinement - in order to highlight the diversity of
functions that microglia perform in building a brain. In
reviewing this literature, it becomes obvious that timing
matters, perhaps more so than the nature of the immune
activation itself; largely conserved patterns of microglial
response to diverse insults result in different functional
impacts depending on the stage of brain maturation at the
time of the challenge.},
Doi = {10.1007/7854_2021_242},
Key = {fds359042}
}
@article{fds361152,
Author = {Devlin, BA and Smith, CJ and Bilbo, SD},
Title = {Sickness and the Social Brain: How the Immune System
Regulates Behavior across Species.},
Journal = {Brain, behavior and evolution},
Volume = {97},
Number = {3-4},
Pages = {197-210},
Year = {2022},
Month = {January},
url = {http://dx.doi.org/10.1159/000521476},
Abstract = {Many instances of sickness critically involve the immune
system. The immune system talks to the brain in a
bidirectional loop. This discourse affords the immune system
immense control, such that it can influence behavior and
optimize recovery from illness. These behavioral responses
to infection are called sickness behaviors and can manifest
in many ways, including changes in mood, motivation, or
energy. Fascinatingly, most of these changes are conserved
across species, and most organisms demonstrate some form of
sickness behaviors. One of the most interesting sickness
behaviors, and not immediately obvious, is altered
sociability. Here, we discuss how the immune system impacts
social behavior, by examining the brain regions and immune
mediators involved in this process. We first outline how
social behavior changes in response to infection in various
species. Next, we explore which brain regions control social
behavior and their evolutionary origins. Finally, we
describe which immune mediators establish the link between
illness and social behavior, in the context of both normal
development and infection. Overall, we hope to make clear
the striking similarities between the mechanisms that
facilitate changes in sociability in derived and ancestral
vertebrate, as well as invertebrate, species.},
Doi = {10.1159/000521476},
Key = {fds361152}
}
@article{fds365998,
Author = {Ceasrine, AM and Devlin, BA and Bolton, JL and Green, LA and Jo, YC and Huynh, C and Patrick, B and Washington, K and Sanchez, CL and Joo, F and Brayan Campos-Salazar and A and Lockshin, ER and Kuhn, C and Murphy, SK and Simmons, LA and Bilbo, SD},
Title = {Maternal diet disrupts the placenta-brain axis in a
sex-specific manner},
Year = {2021},
Month = {November},
url = {http://dx.doi.org/10.1101/2021.11.12.468408},
Abstract = {<jats:title>SUMMARY</jats:title><jats:p>High maternal weight
is associated with a number of detrimental outcomes in
offspring, including increased susceptibility to
neurological disorders such as anxiety, depression, and
communicative disorders (e.g. autism spectrum
disorders)<jats:sup>1–8</jats:sup>. Despite widespread
acknowledgement of sex-biases in the prevalence, incidence,
and age of onset of these disorders, few studies have
investigated potential sex-biased mechanisms underlying
disorder susceptibility. Here, we use a mouse model to
demonstrate how maternal high-fat diet, one contributor to
overweight, causes endotoxin accumulation in fetal tissue,
and subsequent perinatal inflammation influences
sex-specific behavioral outcomes in offspring. In male
high-fat diet offspring, increased macrophage toll like
receptor 4 signaling results in excess phagocytosis of
serotonin neurons in the developing dorsal raphe nucleus,
decreasing serotonin bioavailability in the fetal and adult
brain. Bulk sequencing from a large cohort of matched first
trimester human fetal brain, placenta, and maternal decidua
samples reveals sex-specific transcriptome-wide changes in
placenta and brain tissue in response to maternal
triglyceride accumulation (a proxy for dietary fat content).
Further, we find that fetal brain serotonin levels decrease
as maternal dietary fat intake increases in males only.
These findings uncover a microglia-dependent mechanism
through which maternal diet may impact offspring
susceptibility for neuropsychiatric disorder development in
a sex-specific manner.</jats:p>},
Doi = {10.1101/2021.11.12.468408},
Key = {fds365998}
}
@article{fds359680,
Author = {Bordt, EA and Shook, LL and Atyeo, C and Pullen, KM and De Guzman and RM and Meinsohn, M-C and Chauvin, M and Fischinger, S and Yockey, LJ and James,
K and Lima, R and Yonker, LM and Fasano, A and Brigida, S and Bebell, LM and Roberts, DJ and Pépin, D and Huh, JR and Bilbo, SD and Li, JZ and Kaimal,
A and Schust, DJ and Gray, KJ and Lauffenburger, D and Alter, G and Edlow,
AG},
Title = {Maternal SARS-CoV-2 infection elicits sexually dimorphic
placental immune responses.},
Journal = {Sci Transl Med},
Volume = {13},
Number = {617},
Pages = {eabi7428},
Year = {2021},
Month = {October},
url = {http://dx.doi.org/10.1126/scitranslmed.abi7428},
Abstract = {There is a persistent bias toward higher prevalence and
increased severity of coronavirus disease 2019 (COVID-19) in
males. Underlying mechanisms accounting for this sex
difference remain incompletely understood. Interferon
responses have been implicated as a modulator of COVID-19
disease in adults and play a key role in the placental
antiviral response. Moreover, the interferon response has
been shown to alter Fc receptor expression and therefore may
affect placental antibody transfer. Here, we examined the
intersection of maternal-fetal antibody transfer,
viral-induced placental interferon responses, and fetal sex
in pregnant women infected with severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor
abundance, interferon-stimulated gene (ISG) expression, and
SARS-CoV-2 antibody transfer were interrogated in 68 human
pregnancies. Sexually dimorphic expression of placental Fc
receptors, ISGs and proteins, and interleukin-10 was
observed after maternal SARS-CoV-2 infection, with
up-regulation of these features in placental tissue of
pregnant individuals with male fetuses. Reduced maternal
SARS-CoV-2–specific antibody titers and impaired placental
antibody transfer were also observed in pregnancies with a
male fetus. These results demonstrate fetal sex-specific
maternal and placental adaptive and innate immune responses
to SARS-CoV-2.},
Doi = {10.1126/scitranslmed.abi7428},
Key = {fds359680}
}
@article{fds358813,
Author = {Figueroa, C and Yang, H and DiSpirito, J and Bourgeois, JR and Kalyanasundaram, G and Doshi, I and Bilbo, SD and Kopec,
AM},
Title = {Morphine exposure alters Fos expression in a sex-, age-, and
brain region-specific manner during adolescence.},
Journal = {Developmental psychobiology},
Volume = {63},
Number = {6},
Pages = {e22186},
Year = {2021},
Month = {September},
url = {http://dx.doi.org/10.1002/dev.22186},
Abstract = {Data in both humans and preclinical animal models clearly
indicate drug exposure during adolescence, when the "reward"
circuitry of the brain develops, increases the risk of
substance use and other mental health disorders later in
life. Human data indicate that different neural and
behavioral sequelae can be observed in early versus late
adolescence. However, most studies with rodent models
examine a single adolescent age compared to a mature adult
age, and often only in males. Herein, we sought to determine
whether the acute response to the opioid morphine would also
differ across adolescence, and by sex. By quantifying Fos
positive cells, a proxy for neural activity, at different
stages during adolescence (pre-, early, mid-, and late
adolescence) and in multiple reward regions (prefrontal
cortex, nucleus accumbens, caudate/putamen), we determined
that the neural response to acute morphine is highly
dependent on adolescent age, sex, and brain region. These
data suggest that heterogeneity in the consequences of
adolescent opioid exposure may be due to age- and
sex-specific developmental profiles in individual reward
processing regions. In future studies, it will be important
to add age within adolescence as an independent variable for
a holistic view of healthy or abnormal reward-related neural
development.},
Doi = {10.1002/dev.22186},
Key = {fds358813}
}
@article{fds358768,
Author = {Ceasrine, AM and Bilbo, SD},
Title = {Primetime for microglia: When stress and infection
collide.},
Journal = {Neuron},
Volume = {109},
Number = {16},
Pages = {2503-2505},
Year = {2021},
Month = {August},
url = {http://dx.doi.org/10.1016/j.neuron.2021.07.023},
Abstract = {Inflammation during critical windows of development
contributes to behavioral affect later in life. In this of
Neuron, Cao et al. (2021) demonstrate a novel mechanism
through which early life Tlr4-dependent inflammation in
microglia permanently alters neuronal function and leaves
male mice susceptible to stress-induced depressive-like
behaviors.},
Doi = {10.1016/j.neuron.2021.07.023},
Key = {fds358768}
}
@article{fds354527,
Author = {Maguire, RL and House, JS and Lloyd, DT and Skinner, HG and Allen, TK and Raffi, AM and Skaar, DA and Park, SS and McCullough, LE and Kollins, SH and Bilbo, SD and Collier, DN and Murphy, SK and Fuemmeler, BF and Gowdy,
KM and Hoyo, C},
Title = {Associations between maternal obesity, gestational cytokine
levels and child obesity in the NEST cohort.},
Journal = {Pediatr Obes},
Volume = {16},
Number = {7},
Pages = {e12763},
Year = {2021},
Month = {July},
url = {http://dx.doi.org/10.1111/ijpo.12763},
Abstract = {BACKGROUND: Although maternal systemic inflammation is
hypothesized to link maternal pre-pregnancy obesity to
offspring metabolic dysfunction, patient empirical data are
limited. OBJECTIVES: In this study, we hypothesized that
pre-pregnancy obesity alters systemic chemo/cytokines
concentrations in pregnancy, and this alteration contributes
to obesity in children. METHODS: In a multi-ethnic cohort of
361 mother-child pairs, we measured prenatal concentrations
of plasma TNF-α, IL-6, IL-8, IL-1β, IL-4, IFN-γ, IL-12
p70 subunit, and IL-17A using a multiplex ELISA and examined
associations of pre-pregnancy obesity on maternal
chemo/cytokine levels, and associations of these cytokine
levels with offspring body mass index z score (BMI-z) at age
2-6 years using linear regression. RESULTS: After
adjusting for maternal smoking, ethnicity, age, and
education, pre-pregnancy obesity was associated with
increased concentrations of TNF-α (P = .026) and IFN-γ
(P = .06). While we found no evidence for associations
between TNF-α concentrations and offspring BMI-z, increased
IFN-γ concentrations were associated with decreased BMI-z
(P = .0002), primarily in Whites (P = .0011). In
addition, increased maternal IL-17A concentrations were
associated with increased BMI-z in offspring (P = .0005)
with stronger associations in African Americans
(P = .0042) than Whites (P = .24). CONCLUSIONS: Data
from this study are consistent with maternal obesity-related
inflammation during pregnancy, increasing the risk of
childhood obesity in an ethnic-specific manner.},
Doi = {10.1111/ijpo.12763},
Key = {fds354527}
}
@article{fds357322,
Author = {Kemény, LV and Robinson, KC and Hermann, AL and Walker, DM and Regan,
S and Yew, YW and Lai, YC and Theodosakis, N and Rivera, PD and Ding, W and Yang, L and Beyer, T and Loh, Y-HE and Lo, JA and van der Sande, AAJ and Sarnie, W and Kotler, D and Hsiao, JJ and Su, MY and Kato, S and Kotler, J and Bilbo, SD and Chopra, V and Salomon, MP and Shen, S and Hoon, DSB and Asgari, MM and Wakeman, SE and Nestler, EJ and Fisher,
DE},
Title = {Vitamin D deficiency exacerbates UV/endorphin and opioid
addiction.},
Journal = {Science advances},
Volume = {7},
Number = {24},
Pages = {eabe4577},
Year = {2021},
Month = {June},
url = {http://dx.doi.org/10.1126/sciadv.abe4577},
Abstract = {The current opioid epidemic warrants a better understanding
of genetic and environmental factors that contribute to
opioid addiction. Here we report an increased prevalence of
vitamin D (VitD) deficiency in patients diagnosed with
opioid use disorder and an inverse and dose-dependent
association of VitD levels with self-reported opioid use. We
used multiple pharmacologic approaches and genetic mouse
models and found that deficiencies in VitD signaling amplify
exogenous opioid responses that are normalized upon
restoration of VitD signaling. Similarly, physiologic
endogenous opioid analgesia and reward responses triggered
by ultraviolet (UV) radiation are repressed by VitD
signaling, suggesting that a feedback loop exists whereby
VitD deficiency produces increased UV/endorphin-seeking
behavior until VitD levels are restored by cutaneous VitD
synthesis. This feedback may carry the evolutionary
advantage of maximizing VitD synthesis. However, unlike UV
exposure, exogenous opioid use is not followed by VitD
synthesis (and its opioid suppressive effects), contributing
to maladaptive addictive behavior.},
Doi = {10.1126/sciadv.abe4577},
Key = {fds357322}
}
@article{fds361153,
Author = {Bordt, EA and Shook, LL and Atyeo, C and Pullen, KM and De Guzman and RM and Meinsohn, M-C and Chauvin, M and Fischinger, S and Yockey, LJ and James,
K and Lima, R and Yonker, LM and Fasano, A and Brigida, S and Bebell, LM and Roberts, DJ and Pépin, D and Huh, JR and Bilbo, SD and Li, JZ and Kaimal,
A and Schust, D and Gray, KJ and Lauffenburger, D and Alter, G and Edlow,
AG},
Title = {Sexually dimorphic placental responses to maternal
SARS-CoV-2 infection.},
Journal = {bioRxiv},
Year = {2021},
Month = {March},
url = {http://dx.doi.org/10.1101/2021.03.29.437516},
Abstract = {There is a persistent male bias in the prevalence and
severity of COVID-19 disease. Underlying mechanisms
accounting for this sex difference remain incompletely
understood. Interferon responses have been implicated as a
modulator of disease in adults, and play a key role in the
placental anti-viral response. Moreover, the interferon
response has been shown to alter Fc-receptor expression, and
therefore may impact placental antibody transfer. Here we
examined the intersection of viral-induced placental
interferon responses, maternal-fetal antibody transfer, and
fetal sex. Placental interferon stimulated genes (ISGs),
Fc-receptor expression, and SARS-CoV-2 antibody transfer
were interrogated in 68 pregnancies. Sexually dimorphic
placental expression of ISGs, interleukin-10, and Fc
receptors was observed following maternal SARS-CoV-2
infection, with upregulation in males. Reduced maternal
SARS-CoV-2-specific antibody titers and impaired placental
antibody transfer were noted in pregnancies with a male
fetus. These results demonstrate fetal sex-specific maternal
and placental adaptive and innate immune responses to
SARS-CoV-2.},
Doi = {10.1101/2021.03.29.437516},
Key = {fds361153}
}
@article{fds355562,
Author = {Smith, CJ and Bilbo, SD},
Title = {Sickness and the Social Brain: Love in the Time of
COVID.},
Journal = {Frontiers in psychiatry},
Volume = {12},
Pages = {633664},
Year = {2021},
Month = {January},
url = {http://dx.doi.org/10.3389/fpsyt.2021.633664},
Abstract = {As a highly social species, inclusion in social networks and
the presence of strong social bonds are critical to our
health and well-being. Indeed, impaired social functioning
is a component of numerous neuropsychiatric disorders
including depression, anxiety, and substance use disorder.
During the current COVID-19 pandemic, our social networks
are at risk of fracture and many are vulnerable to the
negative consequences of social isolation. Importantly,
infection itself leads to changes in social behavior as a
component of "sickness behavior." Furthermore, as in the
case of COVID-19, males and females often differ in their
immunological response to infection, and, therefore, in
their susceptibility to negative outcomes. In this review,
we discuss the many ways in which infection changes social
behavior-sometimes to the benefit of the host, and in some
instances for the sake of the pathogen-in species ranging
from eusocial insects to humans. We also explore the
neuroimmune mechanisms by which these changes in social
behavior occur. Finally, we touch upon the ways in which the
social environment (group living, social isolation, etc.)
shapes the immune system and its ability to respond to
challenge. Throughout we emphasize how males and females
differ in their response to immune activation, both
behaviorally and physiologically.},
Doi = {10.3389/fpsyt.2021.633664},
Key = {fds355562}
}
@article{fds352331,
Author = {Smith, CJ and Kingsbury, MA and Dziabis, JE and Hanamsagar, R and Malacon, KE and Tran, JN and Norris, HA and Gulino, M and Bordt, EA and Bilbo, SD},
Title = {Neonatal immune challenge induces female-specific changes in
social behavior and somatostatin cell number.},
Journal = {Brain, behavior, and immunity},
Volume = {90},
Pages = {332-345},
Year = {2020},
Month = {November},
url = {http://dx.doi.org/10.1016/j.bbi.2020.08.013},
Abstract = {Decreases in social behavior are a hallmark aspect of acute
"sickness behavior" in response to infection. However,
immune insults that occur during the perinatal period may
have long-lasting consequences for adult social behavior by
impacting the developmental organization of underlying
neural circuits. Microglia, the resident immune cells of the
central nervous system, are sensitive to immune stimulation
and play a critical role in the developmental sculpting of
neural circuits, making them likely mediators of this
process. Here, we investigated the impact of a postnatal day
(PND) 4 lipopolysaccharide (LPS) challenge on social
behavior in adult mice. Somewhat surprisingly, neonatal LPS
treatment decreased sociability in adult female, but not
male mice. LPS-treated females also displayed reduced social
interaction and social memory in a social discrimination
task as compared to saline-treated females. Somatostatin
(SST) interneurons within the anterior cingulate cortex
(ACC) have recently been suggested to modulate a variety of
social behaviors. Interestingly, the female-specific changes
in social behavior observed here were accompanied by an
increase in SST interneuron number in the ACC. Finally,
these changes in social behavior and SST cell number do not
appear to depend on microglial inflammatory signaling,
because microglia-specific genetic knock-down of myeloid
differentiation response protein 88 (MyD88; the removal of
which prevents LPS from increasing proinflammatory cytokines
such as TNFα and IL-1β) did not prevent these LPS-induced
changes. This study provides novel evidence for enduring
effects of neonatal immune activation on social behavior and
SST interneurons in females, largely independent of
microglial inflammatory signaling.},
Doi = {10.1016/j.bbi.2020.08.013},
Key = {fds352331}
}
@article{fds340827,
Author = {Missig, G and Robbins, JO and Mokler, EL and McCullough, KM and Bilbo,
SD and McDougle, CJ and Carlezon, WA},
Title = {Sex-dependent neurobiological features of prenatal immune
activation via TLR7.},
Journal = {Molecular psychiatry},
Volume = {25},
Number = {10},
Pages = {2330-2341},
Year = {2020},
Month = {October},
url = {http://dx.doi.org/10.1038/s41380-018-0346-4},
Abstract = {Immune activation during pregnancy via infection or
autoimmune disease is a risk factor for neuropsychiatric
illness. Mouse models of prenatal immune activation often
involve maternal administration of agents that activate
toll-like receptors (TLRs), a class of pattern recognition
receptors that initiate innate immune responses. Such
studies have focused primarily on activating the TLR3 or
TLR4 subtypes, to mimic immune responses to viral or
bacterial infections, respectively. Here, we characterize
the effects of prenatal activation of TLR7, which is
implicated in the pathogenesis of autoimmune disease.
Prenatal TLR7 activation via administration of the selective
agonist imiquimod (5.0 mg/kg) induces a phenotype in
offspring characterized by reduced anxiety-like behavior,
fragmented social behavior, and altered ultrasonic
vocalization patterns at 6-12 weeks of age. The
characteristics of this phenotype are readily
distinguishable from-and in some ways opposite to-those seen
following prenatal activation of TLR3 and/or TLR4. Prenatal
TLR7-activated mice have normal baseline locomotor activity,
but are hyperresponsive to stimuli including social
partners, circadian cues, and gonadal hormone fluctuations.
These alterations are accompanied by decreases in microglia
density but increases in ramifications. RNA-sequencing of
dorsal striatum, a region showing profound changes in
microglial markers, indicates that prenatal TLR7 activation
induces differential expression of hundreds of genes at 13
weeks of age, with virtually no overlap in differentially
expressed genes between males and females. Our findings
demonstrate that prenatal immune activation can promote a
wide range of developmental trajectories, depending on the
type and/or pattern of TLR activation and the sex of the
offspring.},
Doi = {10.1038/s41380-018-0346-4},
Key = {fds340827}
}
@article{fds347134,
Author = {Bordt, EA and Ceasrine, AM and Bilbo, SD},
Title = {Microglia and sexual differentiation of the developing
brain: A focus on ontogeny and intrinsic
factors.},
Journal = {Glia},
Volume = {68},
Number = {6},
Pages = {1085-1099},
Year = {2020},
Month = {June},
url = {http://dx.doi.org/10.1002/glia.23753},
Abstract = {Sexual differentiation of the brain during early development
likely underlies the strong sex biases prevalent in many
neurological conditions. Mounting evidence indicates that
microglia, the innate immune cells of the central nervous
system, are intricately involved in these sex-specific
processes of differentiation. In this review, we synthesize
literature demonstrating sex differences in microglial
number, morphology, transcriptional state, and functionality
throughout spatiotemporal development as well as highlight
current literature regarding ontogeny of microglia. Along
with vanRyzin et al. in this issue, we explore the idea that
differences in microglia imparted by chromosomal or
ontogeny-related programming can influence microglial-driven
sexual differentiation of the brain, as well as the idea
that extrinsic differences in the male and female brain
microenvironment may in turn impart sex differences in
microglia.},
Doi = {10.1002/glia.23753},
Key = {fds347134}
}
@article{fds348872,
Author = {Hollander, JA and Cory-Slechta, DA and Jacka, FN and Szabo, ST and Guilarte, TR and Bilbo, SD and Mattingly, CJ and Moy, SS and Haroon, E and Hornig, M and Levin, ED and Pletnikov, MV and Zehr, JL and McAllister,
KA and Dzierlenga, AL and Garton, AE and Lawler, CP and Ladd-Acosta,
C},
Title = {Beyond the looking glass: recent advances in understanding
the impact of environmental exposures on neuropsychiatric
disease.},
Journal = {Neuropsychopharmacology},
Volume = {45},
Number = {7},
Pages = {1086-1096},
Year = {2020},
Month = {June},
url = {http://dx.doi.org/10.1038/s41386-020-0648-5},
Abstract = {The etiologic pathways leading to neuropsychiatric diseases
remain poorly defined. As genomic technologies have advanced
over the past several decades, considerable progress has
been made linking neuropsychiatric disorders to genetic
underpinnings. Interest and consideration of nongenetic risk
factors (e.g., lead exposure and schizophrenia) have, in
contrast, lagged behind heritable frameworks of explanation.
Thus, the association of neuropsychiatric illness to
environmental chemical exposure, and their potential
interactions with genetic susceptibility, are largely
unexplored. In this review, we describe emerging approaches
for considering the impact of chemical risk factors acting
alone and in concert with genetic risk, and point to the
potential role of epigenetics in mediating exposure effects
on transcription of genes implicated in mental disorders. We
highlight recent examples of research in nongenetic risk
factors in psychiatric disorders that point to potential
shared biological mechanisms-synaptic dysfunction, immune
alterations, and gut-brain interactions. We outline new
tools and resources that can be harnessed for the study of
environmental factors in psychiatric disorders. These tools,
combined with emerging experimental evidence, suggest that
there is a need to broadly incorporate environmental
exposures in psychiatric research, with the ultimate goal of
identifying modifiable risk factors and informing new
treatment strategies for neuropsychiatric
disease.},
Doi = {10.1038/s41386-020-0648-5},
Key = {fds348872}
}
@article{fds357323,
Author = {Bordt, EA and Block, CL and Petrozziello, T and Sadri-Vakili, G and Smith, CJ and Edlow, AG and Bilbo, SD},
Title = {Isolation of Microglia from Mouse or Human
Tissue.},
Journal = {STAR protocols},
Volume = {1},
Number = {1},
Pages = {100035},
Year = {2020},
Month = {June},
url = {http://dx.doi.org/10.1016/j.xpro.2020.100035},
Abstract = {Microglia are the innate immune cells of the central nervous
system. Although numerous methods have been developed to
isolate microglia from the brain, the method of dissociation
and isolation can have a profound effect on the function of
these highly dynamic cells. Here, we present an optimized
protocol to isolate CD11b+ cells (microglia) from mouse or
human brain tissue using magnetic bead columns. Isolated
microglia can be used to model diseases with
neuroinflammatory components for potential therapeutic
discoveries. For complete details on the use and execution
of this protocol, please refer to Hanamsagar et al. (2017),
Rivera et al. (2019), and Edlow et al. (2019).},
Doi = {10.1016/j.xpro.2020.100035},
Key = {fds357323}
}
@article{fds348031,
Author = {Bordt, EA and Bilbo, SD},
Title = {Stressed-Out T Cells Fragment the Mind.},
Journal = {Trends in immunology},
Volume = {41},
Number = {2},
Pages = {94-97},
Year = {2020},
Month = {February},
url = {http://dx.doi.org/10.1016/j.it.2019.12.008},
Abstract = {The immune system is increasingly recognized to play an
integral role in regulating stress responses. In a recent
article in Cell, Fan et al. demonstrate a novel mechanism
through which stress drives mitochondrial
fragmentation-induced xanthine accumulation in mouse
CD4<sup>+</sup> T cells, subsequently acting on
oligodendrocytes to induce anxiety-like behaviors.},
Doi = {10.1016/j.it.2019.12.008},
Key = {fds348031}
}
@article{fds340068,
Author = {Edlow, AG and Glass, RM and Smith, CJ and Tran, PK and James, K and Bilbo,
S},
Title = {Placental Macrophages: A Window Into Fetal Microglial
Function in Maternal Obesity.},
Journal = {International journal of developmental neuroscience : the
official journal of the International Society for
Developmental Neuroscience},
Volume = {77},
Pages = {60-68},
Publisher = {Elsevier BV},
Year = {2019},
Month = {October},
url = {http://dx.doi.org/10.1016/j.ijdevneu.2018.11.004},
Abstract = {Fetal placental macrophages and microglia (resident brain
macrophages) have a common origin in the fetal yolk sac.
Yolk-sac-derived macrophages comprise the permanent pool of
brain microglia throughout an individual's lifetime.
Inappropriate fetal microglial priming may therefore have
lifelong neurodevelopmental consequences, but direct
evaluation of microglial function in a living fetus or
neonate is impossible. We sought to test the hypothesis that
maternal obesity would prime both placental macrophages and
fetal brain microglia to overrespond to an immune challenge,
thus providing a window into microglial function using
placental cells. Obesity was induced in C57BL/6 J mice
using a 60% high-fat diet. On embryonic day 17.5, fetal
brain microglia and corresponding CD11b + placental
cells were isolated from fresh tissue. Cells were treated
with media or lipopolysaccharide (LPS). Tumor necrosis
factor-alpha (TNF-α) production by stimulated and
unstimulated cells was quantified via ELISA. We demonstrate
for the first time that the proinflammatory cytokine
production of CD11b + placental cells is strongly
correlated with that of brain microglia (Spearman's
ρ = 0.73, p = 0.002) in the setting of maternal
obesity. Maternal obesity-exposed CD11b + cells had an
exaggerated response to LPS compared to controls, with a
5.1-fold increase in TNF-α production in placentas
(p = 0.003) and 3.8-fold increase in TNF-α production
in brains (p = 0.002). In sex-stratified analyses, only
male obesity-exposed brains and placentas had significant
increase in TNF-α production in response to LPS. Taken
together, these data suggest that maternal obesity primes
both placental macrophages and fetal brain microglia to
overproduce a proinflammatory cytokine in response to immune
challenge. Male brain and placental immune response is more
marked than female in this setting. Given that fetal
microglial priming may impact neuroimmune function
throughout the lifespan, these data could provide insight
into the male predominance of certain neurodevelopmental
morbidities linked to maternal obesity, including cognitive
dysfunction, autism spectrum disorder, and ADHD. Placental
CD11b+ macrophages may have the potential to serve as an
accessible biomarker of aberrant fetal brain immune
activation in maternal obesity. This finding may have
broader implications for assaying the impact of other
maternal exposures on fetal brain development.},
Doi = {10.1016/j.ijdevneu.2018.11.004},
Key = {fds340068}
}
@article{fds346774,
Author = {Kingsbury, MA and Bilbo, SD},
Title = {The inflammatory event of birth: How oxytocin signaling may
guide the development of the brain and gastrointestinal
system.},
Journal = {Frontiers in neuroendocrinology},
Volume = {55},
Pages = {100794},
Year = {2019},
Month = {October},
url = {http://dx.doi.org/10.1016/j.yfrne.2019.100794},
Abstract = {The role of oxytocin (OT) as a neuropeptide that modulates
social behavior has been extensively studied and reviewed,
but beyond these functions, OT's adaptive functions at birth
are quite numerous, as OT coordinates many physiological
processes in the mother and fetus to ensure a successful
delivery. In this review we explore in detail the potential
adaptive roles of oxytocin as an anti-inflammatory,
protective molecule at birth for the developing fetal brain
and gastrointestinal system based on evidence that birth is
a potent inflammatory/immune event. We discuss data with
relevance for a number of neurodevelopmental disorders, as
well as the emerging role of the gut-brain axis for health
and disease. Finally, we discuss the potential relevance of
sex differences in OT signaling present at birth in the
increased male vulnerability to neurodevelopmental
disabilities.},
Doi = {10.1016/j.yfrne.2019.100794},
Key = {fds346774}
}
@article{fds339550,
Author = {Bordt, EA and Smith, CJ and Demarest, TG and Bilbo, SD and Kingsbury,
MA},
Title = {Mitochondria, Oxytocin, and Vasopressin: Unfolding the
Inflammatory Protein Response.},
Journal = {Neurotoxicity research},
Volume = {36},
Number = {2},
Pages = {239-256},
Year = {2019},
Month = {August},
url = {http://dx.doi.org/10.1007/s12640-018-9962-7},
Abstract = {Neuroendocrine and immune signaling pathways are activated
following insults such as stress, injury, and infection, in
a systemic response aimed at restoring homeostasis.
Mitochondrial metabolism and function have been implicated
in the control of immune responses. Commonly studied along
with mitochondrial function, reactive oxygen species (ROS)
are closely linked to cellular inflammatory responses. It is
also accepted that cells experiencing mitochondrial or
endoplasmic reticulum (ER) stress induce response pathways
in order to cope with protein-folding dysregulation, in
homeostatic responses referred to as the unfolded protein
responses (UPRs). Recent reports indicate that the UPRs may
play an important role in immune responses. Notably, the
homeostasis-regulating hormones oxytocin (OXT) and
vasopressin (AVP) are also associated with the regulation of
inflammatory responses and immune function. Intriguingly,
OXT and AVP have been linked with ER unfolded protein
responses (UPR<sup>ER</sup>), and can impact ROS production
and mitochondrial function. Here, we will review the
evidence for interactions between these various factors and
how these neuropeptides might influence mitochondrial
processes.},
Doi = {10.1007/s12640-018-9962-7},
Key = {fds339550}
}
@article{fds342605,
Author = {Smith, CJ and Bhanot, A and Norman, E and Mullett, JE and Bilbo, SD and McDougle, CJ and Zürcher, NR and Hooker, JM},
Title = {A Protocol for Sedation Free MRI and PET Imaging in Adults
with Autism Spectrum Disorder.},
Journal = {Journal of autism and developmental disorders},
Volume = {49},
Number = {7},
Pages = {3036-3044},
Year = {2019},
Month = {July},
url = {http://dx.doi.org/10.1007/s10803-019-04010-3},
Abstract = {Imaging technologies such as positron emission tomography
(PET) and magnetic resonance imaging (MRI) present
unparalleled opportunities to investigate the neural basis
of autism spectrum disorder (ASD). However, challenges such
as deficits in social interaction, anxiety around new
experiences, impaired language abilities, and
hypersensitivity to sensory stimuli make participating in
neuroimaging studies challenging for individuals with ASD.
In this commentary, we describe the existent training
protocols for preparing individuals with ASD for PET/MRI
scans and our own experience developing a training protocol
to facilitate the inclusion of low-functioning adults with
ASD in PET-MRI studies. We hope to raise awareness of the
need for more information exchange between research groups
about lessons learned in this context in order to include
the entire disease spectrum in neuroimaging
studies.},
Doi = {10.1007/s10803-019-04010-3},
Key = {fds342605}
}
@article{fds342148,
Author = {Kopec, AM and Smith, CJ and Bilbo, SD},
Title = {Neuro-Immune Mechanisms Regulating Social Behavior: Dopamine
as Mediator?},
Journal = {Trends in neurosciences},
Volume = {42},
Number = {5},
Pages = {337-348},
Year = {2019},
Month = {May},
url = {http://dx.doi.org/10.1016/j.tins.2019.02.005},
Abstract = {Social interactions are fundamental to survival and overall
health. The mechanisms underlying social behavior are
complex, but we now know that immune signaling plays a
fundamental role in the regulation of social interactions.
Prolonged or exaggerated alterations in social behavior
often accompany altered immune signaling and function in
pathological states. Thus, unraveling the link between
social behavior and immune signaling is a fundamental
challenge, not only to advance our understanding of human
health and development, but for the design of comprehensive
therapeutic approaches for neural disorders. In this review,
we synthesize literature demonstrating the bidirectional
relationship between social behavior and immune signaling
and highlight recent work linking social behavior, immune
function, and dopaminergic signaling in adolescent neural
and behavioral development.},
Doi = {10.1016/j.tins.2019.02.005},
Key = {fds342148}
}
@article{fds342359,
Author = {Smith, CJ and Bilbo, SD},
Title = {Microglia Sculpt Sex Differences in Social
Behavior.},
Journal = {Neuron},
Volume = {102},
Number = {2},
Pages = {275-277},
Year = {2019},
Month = {April},
url = {http://dx.doi.org/10.1016/j.neuron.2019.03.039},
Abstract = {Microglia are increasingly recognized as developmental
sculptors of neural circuits. In this issue of Neuron,
VanRyzin et al. (2019) demonstrate a novel mechanism by
which endocannabinoids drive microglia to phagocytose
newborn astrocytes in the medial amygdala of male rats,
promoting sex differences in social play
behavior.},
Doi = {10.1016/j.neuron.2019.03.039},
Key = {fds342359}
}
@article{fds342606,
Author = {Edlow, AG and Glass, RM and Bilbo, SD},
Title = {Sexually-Dimorphic Effects of Maternal Obesity on Microglial
Antigen Density in the Embryonic Hippocampus: Implications
for Offspring Hippocampal Learning.},
Journal = {REPRODUCTIVE SCIENCES},
Volume = {26},
Pages = {96A-96A},
Publisher = {SAGE PUBLICATIONS INC},
Year = {2019},
Month = {March},
Key = {fds342606}
}
@article{fds341885,
Author = {Liu, X and Nemeth, DP and McKim, DB and Zhu, L and DiSabato, DJ and Berdysz, O and Gorantla, G and Oliver, B and Witcher, KG and Wang, Y and Negray, CE and Vegesna, RS and Sheridan, JF and Godbout, JP and Robson,
MJ and Blakely, RD and Popovich, PG and Bilbo, SD and Quan,
N},
Title = {Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the
Brain Regulates Distinct Neuroimmune Activities.},
Journal = {Immunity},
Volume = {50},
Number = {3},
Pages = {764-766},
Year = {2019},
Month = {March},
url = {http://dx.doi.org/10.1016/j.immuni.2019.02.012},
Abstract = {© 2019 (Immunity 50, 317-333.e1–e6; February 19, 2019)
Main Text: In the original version of the published
manuscript, the insets of Figure 3F (middle and right
panels) were identical to the insets of Figure 3E. This
error was generated inadvertently during the revision
process of the manuscript. The insets of Figure 3F (middle
and right panels) have now been replaced and are consistent
with their corresponding images, and the revised version is
provided below and has been corrected online. The authors
apologize for the error. [Figure presented]},
Doi = {10.1016/j.immuni.2019.02.012},
Key = {fds341885}
}
@article{fds341510,
Author = {Liu, X and Nemeth, DP and McKim, DB and Zhu, L and DiSabato, DJ and Berdysz, O and Gorantla, G and Oliver, B and Witcher, KG and Wang, Y and Negray, CE and Vegesna, RS and Sheridan, JF and Godbout, JP and Robson,
MJ and Blakely, RD and Popovich, PG and Bilbo, SD and Quan,
N},
Title = {Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the
Brain Regulates Distinct Neuroimmune Activities.},
Journal = {Immunity},
Volume = {50},
Number = {2},
Pages = {317-333.e6},
Year = {2019},
Month = {February},
url = {http://dx.doi.org/10.1016/j.immuni.2018.12.012},
Abstract = {Interleukin-1 (IL-1) signaling is important for multiple
potentially pathogenic processes in the central nervous
system (CNS), but the cell-type-specific roles of IL-1
signaling are unclear. We used a genetic knockin reporter
system in mice to track and reciprocally delete or express
IL-1 receptor 1 (IL-1R1) in specific cell types, including
endothelial cells, ventricular cells, peripheral myeloid
cells, microglia, astrocytes, and neurons. We found that
endothelial IL-1R1 was necessary and sufficient for
mediating sickness behavior and drove leukocyte recruitment
to the CNS and impaired neurogenesis, whereas ventricular
IL-1R1 was critical for monocyte recruitment to the CNS.
Although microglia did not express IL-1R1, IL-1 stimulation
of endothelial cells led to the induction of IL-1 in
microglia. Together, these findings describe the structure
and functions of the brain's IL-1R1-expressing system and
lay a foundation for the dissection and identification of
IL-1R1 signaling pathways in the pathogenesis of CNS
diseases.},
Doi = {10.1016/j.immuni.2018.12.012},
Key = {fds341510}
}
@article{fds339917,
Author = {Rivera, PD and Hanamsagar, R and Kan, MJ and Tran, PK and Stewart, D and Jo, YC and Gunn, M and Bilbo, SD},
Title = {Removal of microglial-specific MyD88 signaling alters
dentate gyrus doublecortin and enhances opioid
addiction-like behaviors.},
Journal = {Brain Behav Immun},
Volume = {76},
Pages = {104-115},
Year = {2019},
Month = {February},
url = {http://dx.doi.org/10.1016/j.bbi.2018.11.010},
Abstract = {Drugs of abuse promote a potent immune response in central
nervous system (CNS) via the activation of microglia and
astrocytes. However, the molecular mechanisms underlying
microglial activation during addiction are not well known.
We developed and functionally characterized a novel
transgenic mouse (Cx3cr1-CreBTtg/0:MyD88f/f [Cretg/0])
wherein the immune signaling adaptor gene, MyD88, was
specifically deleted in microglia. To test the downstream
effects of loss of microglia-specific MyD88 signaling in
morphine addiction, Cretg/0 and Cre0/0 mice were tested for
reward learning, extinction, and reinstatement using a
conditioned place preference (CPP) paradigm. There were no
differences in drug acquisition, but Cretg/0 mice had
prolonged extinction and enhanced reinstatement compared to
Cre0/0 controls. Furthermore, morphine-treated Cretg/0 mice
showed increased doublecortin (DCX) signal relative to
Cre0/0 control mice in the hippocampus, indicative of
increased number of immature neurons. Additionally, there
was an increase in colocalization of microglial lysosomal
marker CD68 with DCX+cells in morphine-treated Cretg/0 mice
but not in Cre0/0 or drug-naїve mice, suggesting a specific
role for microglial MyD88 signaling in neuronal phagocytosis
in the hippocampus. Our results show that MyD88 deletion in
microglia may negatively impact maturing neurons within the
adult hippocampus and thus reward memories, suggesting a
novel protective role for microglia in opioid
addiction.},
Doi = {10.1016/j.bbi.2018.11.010},
Key = {fds339917}
}
@article{fds339552,
Author = {Kentner, AC and Bilbo, SD and Brown, AS and Hsiao, EY and McAllister,
AK and Meyer, U and Pearce, BD and Pletnikov, MV and Yolken, RH and Bauman,
MD},
Title = {Maternal immune activation: reporting guidelines to improve
the rigor, reproducibility, and transparency of the
model.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {44},
Number = {2},
Pages = {245-258},
Year = {2019},
Month = {January},
url = {http://dx.doi.org/10.1038/s41386-018-0185-7},
Abstract = {The 2017 American College of Neuropychopharmacology (ACNP)
conference hosted a Study Group on 4 December 2017,
Establishing best practice guidelines to improve the rigor,
reproducibility, and transparency of the maternal immune
activation (MIA) animal model of neurodevelopmental
abnormalities. The goals of this session were to (a)
evaluate the current literature and establish a consensus on
best practices to be implemented in MIA studies, (b)
identify remaining research gaps warranting additional data
collection and lend to the development of evidence-based
best practice design, and (c) inform the MIA research
community of these findings. During this session, there was
a detailed discussion on the importance of validating
immunogen doses and standardizing the general design (e.g.,
species, immunogenic compound used, housing) of our MIA
models both within and across laboratories. The consensus of
the study group was that data does not currently exist to
support specific evidence-based model selection or
methodological recommendations due to lack of consistency in
reporting, and that this issue extends to other inflammatory
models of neurodevelopmental abnormalities. This launched a
call to establish a reporting checklist focusing on
validation, implementation, and transparency modeled on the
ARRIVE Guidelines and CONSORT (scientific reporting
guidelines for animal and clinical research, respectively).
Here we provide a summary of the discussions in addition to
a suggested checklist of reporting guidelines needed to
improve the rigor and reproducibility of this valuable
translational model, which can be adapted and applied to
other animal models as well.},
Doi = {10.1038/s41386-018-0185-7},
Key = {fds339552}
}
@article{fds339551,
Author = {Kopec, AM and Smith, CJ and Ayre, NR and Sweat, SC and Bilbo,
SD},
Title = {Microglial dopamine receptor elimination defines
sex-specific nucleus accumbens development and social
behavior in adolescent rats.},
Journal = {Nature communications},
Volume = {9},
Number = {1},
Pages = {3769},
Year = {2018},
Month = {September},
url = {http://dx.doi.org/10.1038/s41467-018-06118-z},
Abstract = {Adolescence is a developmental period in which the
mesolimbic dopaminergic "reward" circuitry of the brain,
including the nucleus accumbens (NAc), undergoes significant
plasticity. Dopamine D1 receptors (D1rs) in the NAc are
critical for social behavior, but how these receptors are
regulated during adolescence is not well understood. In this
report, we demonstrate that microglia and
complement-mediated phagocytic activity shapes NAc
development by eliminating D1rs in male, but not female
rats, during adolescence. Moreover, immune-mediated
elimination of D1rs is required for natural developmental
changes in male social play behavior. These data demonstrate
for the first time that microglia and complement-mediated
immune signaling (i) participate in adolescent brain
development in a sex-specific manner, and (ii) are causally
implicated in developmental changes in behavior. These data
have broad implications for understanding the adolescent
critical period of development, the molecular mechanisms
underlying social behavior, and sex differences in brain
structure and function.},
Doi = {10.1038/s41467-018-06118-z},
Key = {fds339551}
}
@article{fds339553,
Author = {Bilbo, SD},
Title = {The diverse culinary habits of microglia.},
Journal = {Nature neuroscience},
Volume = {21},
Number = {8},
Pages = {1023-1025},
Year = {2018},
Month = {August},
url = {http://dx.doi.org/10.1038/s41593-018-0196-z},
Doi = {10.1038/s41593-018-0196-z},
Key = {fds339553}
}
@article{fds339554,
Author = {Kopec, AM and Fiorentino, MR and Bilbo, SD},
Title = {Gut-immune-brain dysfunction in Autism: Importance of
sex.},
Journal = {Brain research},
Volume = {1693},
Number = {Pt B},
Pages = {214-217},
Year = {2018},
Month = {August},
url = {http://dx.doi.org/10.1016/j.brainres.2018.01.009},
Abstract = {Autism Spectrum Disorder (ASD) is characterized by social
behavior deficits, stereotypies, cognitive rigidity, and in
some cases severe intellectual impairment and developmental
delay. Although ASD is most widely identified by its
neurological deficits, gastrointestinal issues are common in
ASD. An intimate and complex relationship exists between the
gut, the immune system, and the brain, leading to the
hypothesis that ASD may be a systems-level disease affecting
the gut and immune systems, in addition to the brain.
Despite significant advances in understanding the
contribution of the gut and immune systems to the etiology
of ASD, there is an intriguing commonality among patients
that is not well understood: they are predominantly male.
Virtually no attention has been given to the potential role
of sex-specific regulation of gut, peripheral, and central
immune function in ASD, despite the 4:1 male-to-female bias
in this disorder. In this review, we discuss recent
revelations regarding the impact of gut-immune-brain
relationships on social behavior in rodent models and in ASD
patients, placing them in the context of known or putative
sex specific mechanisms.},
Doi = {10.1016/j.brainres.2018.01.009},
Key = {fds339554}
}
@article{fds366410,
Author = {Dozmorov, MG and Bilbo, SD and Kollins, SH and Zucker, N and Do, EK and Schechter, JC and Zhang, JJ and Murphy, SK and Hoyo, C and Fuemmeler,
BF},
Title = {Associations between maternal cytokine levels during
gestation and measures of child cognitive abilities and
executive functioning.},
Journal = {Brain Behav Immun},
Volume = {70},
Pages = {390-397},
Year = {2018},
Month = {May},
url = {http://dx.doi.org/10.1016/j.bbi.2018.03.029},
Abstract = {Preclinical studies demonstrate that environmentally-induced
alterations in inflammatory cytokines generated by the
maternal and fetal immune system can significantly impact
fetal brain development. Yet, the relationship between
maternal cytokines during gestation and later cognitive
ability and executive function remains understudied.
Children (n = 246) were born of mothers enrolled in the
Newborn Epigenetic Study - a prospective pre-birth cohort in
the Southeastern US. We characterized seven cytokines
[IL-1β, IL-4,IL-6, IL-12p70, IL-17A, tumor necrosis
factor-α (TNFα), and interferon-γ (IFNγ)] and one
chemokine (IL-8) from maternal plasma collected during
pregnancy. We assessed children's cognitive abilities and
executive functioning at a mean age of 4.5 (SD = 1.1)
years. Children's DAS-II and NIH toolbox scores were
regressed on cytokines and the chemokine, controlling for
maternal age, race, education, body mass index, IQ, parity,
smoking status, delivery type, gestational weeks, and child
birth weight and sex. Higher IL-12p70 (βIL-12p70 = 4.26,
p = 0.023) and IL-17A (βIL-17A = 3.70, p = 0.042)
levels were related to higher DAS-II GCA score, whereas
higher IL-1β (βIL-1B = -6.07, p = 0.003) was related
to lower GCA score. Higher IL-12p70 was related to higher
performance on NIH toolbox measures of executive functions
related to inhibitory control and attention (βIL-12p70 =
5.20, p = 0.046) and cognitive flexibility (βIL-12p70 =
5.10, p = 0.047). Results suggest that dysregulation in
gestational immune activity are associated with child
cognitive ability and executive functioning.},
Doi = {10.1016/j.bbi.2018.03.029},
Key = {fds366410}
}
@article{fds339722,
Author = {Bilbo, SD},
Title = {Sex Differences Shape Brain Development and Function, in
Health and Disease: Policy Implications},
Journal = {Policy Insights from the Behavioral and Brain
Sciences},
Volume = {5},
Number = {1},
Pages = {104-109},
Publisher = {SAGE Publications},
Year = {2018},
Month = {March},
url = {http://dx.doi.org/10.1177/2372732217742673},
Abstract = {Sex differences profoundly impact health and disease.
Despite this, the inclusion of females in clinical and
fundamental research lags far behind advances in other
aspects of medicine, especially in the brain sciences.
Regardless of whether neuroscientists are intrinsically
interested in sex differences per se, observing a sex
disparity in the incidence or presentation of a given
neurological disorder provides a significant clue into the
neurobiology of that disorder. Autism spectrum disorder
(ASD) is one of the most sex-biased disorders, with a 4:1
male-to-female ratio, an important aspect of its etiology
and biology that has largely been ignored in the preclinical
literature. This article briefly overviews what is known
about the sexual differentiation of the developing healthy
brain, with a focus on the preclinical literature. This
places observed sex differences in neurological disorders
such as ASD into the context of known sex differences in
neurobiology—along with insight from known sex-specific
mechanisms in other systems that impact the brain (e.g.,
immune system, microbiome). Finally, the article provides
recommendations for progress forward.},
Doi = {10.1177/2372732217742673},
Key = {fds339722}
}
@article{fds342607,
Author = {Hanamsagar, R and Alter, MD and Block, CS and Sullivan, H and Bolton,
JL and Bilbo, SD},
Title = {Generation of a microglial developmental index in mice and
in humans reveals a sex difference in maturation and immune
reactivity.},
Journal = {Glia},
Volume = {66},
Number = {2},
Pages = {460},
Year = {2018},
Month = {February},
url = {http://dx.doi.org/10.1002/glia.23277},
Doi = {10.1002/glia.23277},
Key = {fds342607}
}
@article{fds339555,
Author = {Bilbo, SD and Block, CL and Bolton, JL and Hanamsagar, R and Tran,
PK},
Title = {Beyond infection - Maternal immune activation by
environmental factors, microglial development, and relevance
for autism spectrum disorders.},
Journal = {Experimental neurology},
Volume = {299},
Number = {Pt A},
Pages = {241-251},
Year = {2018},
Month = {January},
url = {http://dx.doi.org/10.1016/j.expneurol.2017.07.002},
Abstract = {Immune molecules such as cytokines and chemokines and the
cells that produce them within the brain, notably microglia,
are critical for normal brain development. This recognition
has in recent years led to the working hypothesis that
inflammatory events during pregnancy, e.g. in response to
infection, may disrupt the normal expression of immune
molecules during critical stages of neural development and
thereby contribute to the risk for neurodevelopmental
disorders such as autism spectrum disorder (ASD). This
hypothesis has in large part been shepherded by the work of
Dr. Paul Patterson and colleagues, which has elegantly
demonstrated that a single viral infection or injection of a
viral mimetic to pregnant mice significantly and
persistently impacts offspring immune and nervous system
function, changes that underlie ASD-like behavioral
dysfunction including social and communication deficits.
Subsequent studies by many labs - in humans and in non-human
animal models - have supported the hypothesis that ongoing
disrupted immune molecule expression and/or
neuroinflammation contributes to at least a significant
subset of ASD. The heterogeneous clinical and biological
phenotypes observed in ASD strongly suggest that in
genetically susceptible individuals, environmental risk
factors combine or synergize to create a tipping or
threshold point for dysfunction. Importantly, animal studies
showing a link between maternal immune activation (MIA) and
ASD-like outcomes in offspring involve different species and
diverse environmental factors associated with ASD in humans,
beyond infection, including toxin exposures, maternal
stress, and maternal obesity, all of which impact
inflammatory or immune pathways. The goal of this review is
to highlight the broader implications of Dr. Patterson's
work for the field of autism, with a focus on the impact
that MIA by diverse environmental factors has on fetal brain
development, immune system development, and the
pathophysiology of ASD.},
Doi = {10.1016/j.expneurol.2017.07.002},
Key = {fds339555}
}
@article{fds339556,
Author = {Hanamsagar, R and Bilbo, SD},
Title = {Environment matters: microglia function and dysfunction in a
changing world.},
Journal = {Current opinion in neurobiology},
Volume = {47},
Pages = {146-155},
Year = {2017},
Month = {December},
url = {http://dx.doi.org/10.1016/j.conb.2017.10.007},
Abstract = {The immune system is our interface with the environment, and
immune molecules such as cytokines and chemokines and the
cells that produce them within the brain, notably microglia,
are critical for normal brain development. This recognition
has in recent years led to the working hypothesis that
inflammatory events during pregnancy or the early postnatal
period, for example, in response to infection, may disrupt
the normal developmental trajectory of microglia and
consequently their interactions with neurons, thereby
contributing to the risk for neurological disorders. The
current article outlines recent findings on the impact of
diverse, pervasive environmental challenges, beyond
infection, including air pollution and maternal stress; and
their impact on microglial development and its broad
implications for neural pathologies.},
Doi = {10.1016/j.conb.2017.10.007},
Key = {fds339556}
}
@article{fds366411,
Author = {Lacagnina, MJ and Kopec, AM and Cox, SS and Hanamsagar, R and Wells, C and Slade, S and Grace, PM and Watkins, LR and Levin, ED and Bilbo,
SD},
Title = {Opioid Self-Administration is Attenuated by Early-Life
Experience and Gene Therapy for Anti-Inflammatory IL-10 in
the Nucleus Accumbens of Male Rats.},
Journal = {Neuropsychopharmacology},
Volume = {42},
Number = {11},
Pages = {2128-2140},
Year = {2017},
Month = {October},
url = {http://dx.doi.org/10.1038/npp.2017.82},
Abstract = {Early-life conditions can contribute to the propensity for
developing neuropsychiatric disease, including substance
abuse disorders. However, the long-lasting mechanisms that
shape risk or resilience for drug addiction remain unclear.
Previous work has shown that a neonatal handling procedure
in rats (which promotes enriched maternal care) attenuates
morphine conditioning, reduces morphine-induced glial
activation, and increases microglial expression of the
anti-inflammatory cytokine interleukin-10 (IL-10). We thus
hypothesized that anti-inflammatory signaling may underlie
the effects of early-life experience on later-life opioid
drug-taking. Here we demonstrate that neonatal handling
attenuates intravenous self-administration of the opioid
remifentanil in a drug-concentration-dependent manner.
Transcriptional profiling of the nucleus accumbens (NAc)
from handled rats following repeated exposure to
remifentanil reveals a suppression of pro-inflammatory
cytokine and chemokine gene expression, consistent with an
anti-inflammatory phenotype. To determine if
anti-inflammatory signaling alters drug-taking behavior, we
administered intracranial injections of plasmid DNA encoding
IL-10 (pDNA-IL-10) into the NAc of non-handled rats. We
discovered that pDNA-IL-10 treatment reduces remifentanil
self-administration in a drug-concentration-dependent
manner, similar to the effect of handling. In contrast,
neither handling nor pDNA-IL-10 treatment alters
self-administration of food or sucrose rewards. These
collective observations suggest that neuroimmune signaling
mechanisms in the NAc are shaped by early-life experience
and may modify motivated behaviors for opioid drugs.
Moreover, manipulation of the IL-10 signaling pathway
represents a novel approach for influencing opioid
reinforcement.},
Doi = {10.1038/npp.2017.82},
Key = {fds366411}
}
@article{fds366412,
Author = {Bolton, JL and Wiley, MG and Ryan, B and Truong, S and Strait, M and Baker,
DC and Yang, NY and Ilkayeva, O and O'Connell, TM and Wroth, SW and Sánchez, CL and Swamy, G and Newgard, C and Kuhn, C and Bilbo, SD and Simmons, LA},
Title = {Perinatal western-type diet and associated gestational
weight gain alter postpartum maternal mood.},
Journal = {Brain Behav},
Volume = {7},
Number = {10},
Pages = {e00828},
Year = {2017},
Month = {October},
url = {http://dx.doi.org/10.1002/brb3.828},
Abstract = {INTRODUCTION: The role of perinatal diet in postpartum
maternal mood disorders, including depression and anxiety,
remains unclear. We investigated whether perinatal
consumption of a Western-type diet (high in fat and
branched-chain amino acids [BCAA]) and associated
gestational weight gain (GWG) cause serotonin dysregulation
in the central nervous system (CNS), resulting in postpartum
depression and anxiety (PPD/A). METHODS: Mouse dams were fed
one of four diets (high-fat/high BCAA, low-fat/high BCAA,
high-fat, and low-fat) prior to mating and throughout
gestation and lactation. Postpartum behavioral assessments
were conducted, and plasma and brain tissues assayed. To
evaluate potential clinical utility, we conducted
preliminary human studies using data from an extant sample
of 17 primiparous women with high GWG, comparing across
self-reported postpartum mood symptoms using the Edinburgh
Postnatal Depression Scale (EPDS) for percent GWG and plasma
amino acid levels. RESULTS: Mouse dams fed the high-fat/high
BCAA diet gained more weight per kcal consumed, and
BCAA-supplemented dams lost weight more slowly postpartum.
Dams on BCAA-supplemented diets exhibited increased
PPD/A-like behavior, decreased dopaminergic function, and
decreased plasma tyrosine and histidine levels when assessed
on postnatal day (P)8. Preliminary human data showed that
GWG accounted for 29% of the variance in EPDS scores.
Histidine was also lower in women with higher EPDS scores.
CONCLUSIONS: These findings highlight the role of perinatal
diet and excess GWG in the development of postpartum mood
disorders.},
Doi = {10.1002/brb3.828},
Key = {fds366412}
}
@article{fds339557,
Author = {Hanamsagar, R and Alter, MD and Block, CS and Sullivan, H and Bolton,
JL and Bilbo, SD},
Title = {Generation of a microglial developmental index in mice and
in humans reveals a sex difference in maturation and immune
reactivity.},
Journal = {Glia},
Volume = {65},
Number = {9},
Pages = {1504-1520},
Year = {2017},
Month = {September},
url = {http://dx.doi.org/10.1002/glia.23176},
Abstract = {Evidence suggests many neurological disorders emerge when
normal neurodevelopmental trajectories are disrupted, i.e.,
when circuits or cells do not reach their fully mature
state. Microglia play a critical role in normal
neurodevelopment and are hypothesized to contribute to brain
disease. We used whole transcriptome profiling with Next
Generation sequencing of purified developing microglia to
identify a microglial developmental gene expression program
involving thousands of genes whose expression levels change
monotonically (up or down) across development. Importantly,
the gene expression program was delayed in males relative to
females and exposure of adult male mice to LPS, a potent
immune activator, accelerated microglial development in
males. Next, a microglial developmental index (MDI)
generated from gene expression patterns obtained from
purified mouse microglia, was applied to human brain
transcriptome datasets to test the hypothesis that
variability in microglial development is associated with
human diseases such as Alzheimer's and autism where
microglia have been suggested to play a role. MDI was
significantly increased in both Alzheimer's Disease and in
autism, suggesting that accelerated microglial development
may contribute to neuropathology. In conclusion, we
identified a microglia-specific gene expression program in
mice that was used to create a microglia developmental
index, which was applied to human datasets containing
heterogeneous cell types to reveal differences between
healthy and diseased brain samples, and between males and
females. This powerful tool has wide ranging applicability
to examine microglial development within the context of
disease and in response to other variables such as stress
and pharmacological treatments.},
Doi = {10.1002/glia.23176},
Key = {fds339557}
}
@article{fds326608,
Author = {Bilbo, SD},
Title = {Sex differences in microglial appetites during development:
Inferences and implications.},
Journal = {Brain, behavior, and immunity},
Volume = {64},
Pages = {9-10},
Year = {2017},
Month = {August},
url = {http://dx.doi.org/10.1016/j.bbi.2017.05.010},
Doi = {10.1016/j.bbi.2017.05.010},
Key = {fds326608}
}
@article{fds366413,
Author = {McCullough, LE and Miller, EE and Calderwood, LE and Shivappa, N and Steck, SE and Forman, MR and A Mendez and M and Maguire, R and Fuemmeler,
BF and Kollins, SH and D Bilbo and S and Huang, Z and Murtha, AP and Murphy,
SK and Hébert, JR and Hoyo, C},
Title = {Maternal inflammatory diet and adverse pregnancy outcomes:
Circulating cytokines and genomic imprinting as potential
regulators?},
Journal = {Epigenetics},
Volume = {12},
Number = {8},
Pages = {688-697},
Year = {2017},
Month = {August},
url = {http://dx.doi.org/10.1080/15592294.2017.1347241},
Abstract = {Excessive inflammation during pregnancy alters homeostatic
mechanisms of the developing fetus and has been linked to
adverse pregnancy outcomes. An anti-inflammatory diet could
be a promising avenue to combat the pro-inflammatory state
of pregnancy, particularly in obese women, but we lack
mechanistic data linking this dietary pattern during
pregnancy to inflammation and birth outcomes. In an
ethnically diverse cohort of 1057 mother-child pairs, we
estimated the relationships between dietary inflammatory
potential [measured via the energy-adjusted dietary
inflammatory index (E-DII™)] and birth outcomes overall,
as well as by offspring sex and maternal pre-pregnancy body
mass index (BMI). In a subset of women, we also explored
associations between E-DII, circulating cytokines (n = 105),
and offspring methylation (n = 338) as potential modulators
of these relationships using linear regression. Adjusted
regression models revealed that women with pro-inflammatory
diets had elevated rates of preterm birth among female
offspring [β = -0.22, standard error (SE) = 0.07, P<0.01],
but not male offspring (β=0.09, SE = 0.06, P<0.12)
(Pinteraction = 0.003). Similarly, we observed
pro-inflammatory diets were associated with higher rates of
caesarean delivery among obese women (β = 0.17, SE = 0.08,
P = 0.03), but not among women with BMI <25 kg/m2
(Pinteraction = 0.02). We observed consistent inverse
associations between maternal inflammatory cytokine
concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and
lower methylation at the MEG3 regulatory sequence (P<0.05);
however, results did not support the link between maternal
E-DII and circulating cytokines. We replicate work by others
on the association between maternal inflammatory diet and
adverse pregnancy outcomes and provide the first empirical
evidence supporting the inverse association between
circulating cytokine concentrations and offspring
methylation.},
Doi = {10.1080/15592294.2017.1347241},
Key = {fds366413}
}
@article{fds326354,
Author = {Parker, W and Hornik, CD and Bilbo, S and Holzknecht, ZE and Gentry, L and Rao, R and Lin, SS and Herbert, MR and Nevison, CD},
Title = {The role of oxidative stress, inflammation and acetaminophen
exposure from birth to early childhood in the induction of
autism.},
Journal = {J Int Med Res},
Volume = {45},
Number = {2},
Pages = {407-438},
Year = {2017},
Month = {April},
url = {http://dx.doi.org/10.1177/0300060517693423},
Abstract = {The wide range of factors associated with the induction of
autism is invariably linked with either inflammation or
oxidative stress, and sometimes both. The use of
acetaminophen in babies and young children may be much more
strongly associated with autism than its use during
pregnancy, perhaps because of well-known deficiencies in the
metabolic breakdown of pharmaceuticals during early
development. Thus, one explanation for the increased
prevalence of autism is that increased exposure to
acetaminophen, exacerbated by inflammation and oxidative
stress, is neurotoxic in babies and small children. This
view mandates extreme urgency in probing the long-term
effects of acetaminophen use in babies and the possibility
that many cases of infantile autism may actually be induced
by acetaminophen exposure shortly after birth.},
Doi = {10.1177/0300060517693423},
Key = {fds326354}
}
@article{fds325332,
Author = {Kopec, AM and Rivera, PD and Lacagnina, MJ and Hanamsagar, R and Bilbo,
SD},
Title = {Optimized solubilization of TRIzol-precipitated protein
permits Western blotting analysis to maximize data available
from brain tissue.},
Journal = {Journal of neuroscience methods},
Volume = {280},
Pages = {64-76},
Year = {2017},
Month = {March},
url = {http://dx.doi.org/10.1016/j.jneumeth.2017.02.002},
Abstract = {<h4>Background</h4>Techniques simultaneously assessing
multiple levels of molecular processing are appealing
because molecular signaling underlying complex neural
phenomena occurs at complementary levels. The TRIzol method
isolates RNA and DNA, but protein retrieval is difficult due
to inefficient solubilization of precipitated protein
pellets.<h4>New method</h4>We optimized a buffer for the
efficient solubilization of protein from TRIzol-precipitated
brain tissue for Western blotting analysis, which was also
more effective at directly homogenizing brain tissue than
RIPA buffer.<h4>Results</h4>Protein yield during
solubilization, in addition to protein yield via direct
homogenization, is increased by optimizing concentrations of
chemicals in a standard lysis buffer. Effective incubation
parameters for both total protein yield and the analysis of
post-translational modifications is remarkably flexible.
Importantly, different neural cell types and protein classes
are represented in solubilized protein samples. Moreover, we
used dissociated mouse brain tissue to isolate microglia
from other cell types and successfully resolved cell
type-specific proteins from these small and difficult to
attain samples.<h4>Comparison with existing
method(s)</h4>Solubilization buffers to date have been
comprised primarily of SDS or urea; the data herein
demonstrate that components common to lysis buffers can also
enhance protein solubilization both after direct
homogenization and after precipitation.<h4>Conclusions</h4>This
method is suitable for assessing gene and protein expression
from a single brain sample, allowing for a more
comprehensive evaluation of neural phenomena while
minimizing the number of subjects.},
Doi = {10.1016/j.jneumeth.2017.02.002},
Key = {fds325332}
}
@article{fds321831,
Author = {Lacagnina, MJ and Rivera, PD and Bilbo, SD},
Title = {Glial and Neuroimmune Mechanisms as Critical Modulators of
Drug Use and Abuse.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {42},
Number = {1},
Pages = {156-177},
Year = {2017},
Month = {January},
url = {http://dx.doi.org/10.1038/npp.2016.121},
Abstract = {Drugs of abuse cause persistent alterations in synaptic
plasticity that may underlie addiction behaviors. Evidence
suggests glial cells have an essential and underappreciated
role in the development and maintenance of drug abuse by
influencing neuronal and synaptic functions in multifaceted
ways. Microglia and astrocytes perform critical functions in
synapse formation and refinement in the developing brain,
and there is growing evidence that disruptions in glial
function may be implicated in numerous neurological
disorders throughout the lifespan. Linking evidence of
function in health and under pathological conditions, this
review will outline the glial and neuroimmune mechanisms
that may contribute to drug-abuse liability, exploring
evidence from opioids, alcohol, and psychostimulants. Drugs
of abuse can activate microglia and astrocytes through
signaling at innate immune receptors, which in turn
influence neuronal function not only through secretion of
soluble factors (eg, cytokines and chemokines) but also
potentially through direct remodeling of the synapses. In
sum, this review will argue that neural-glial interactions
represent an important avenue for advancing our
understanding of substance abuse disorders.},
Doi = {10.1038/npp.2016.121},
Key = {fds321831}
}
@article{fds326607,
Author = {Bolton, JL and Marinero, S and Hassanzadeh, T and Natesan, D and Le, D and Belliveau, C and Mason, SN and Auten, RL and Bilbo,
SD},
Title = {Gestational Exposure to Air Pollution Alters Cortical
Volume, Microglial Morphology, and Microglia-Neuron
Interactions in a Sex-Specific Manner.},
Journal = {Frontiers in synaptic neuroscience},
Volume = {9},
Number = {MAY},
Pages = {10},
Year = {2017},
Month = {January},
url = {http://dx.doi.org/10.3389/fnsyn.2017.00010},
Abstract = {Microglia are the resident immune cells of the brain,
important for normal neural development in addition to host
defense in response to inflammatory stimuli. Air pollution
is one of the most pervasive and harmful environmental
toxicants in the modern world, and several large scale
epidemiological studies have recently linked prenatal air
pollution exposure with an increased risk of
neurodevelopmental disorders such as autism spectrum
disorder (ASD). Diesel exhaust particles (DEP) are a primary
toxic component of air pollution, and markedly activate
microglia <i>in vitro</i> and <i>in vivo</i> in adult
rodents. We have demonstrated that <i>prenatal</i> exposure
to DEP in mice, i.e., to the pregnant dams throughout
gestation, results in a persistent vulnerability to
behavioral deficits in adult offspring, especially in males,
which is intriguing given the greater incidence of ASD in
males to females (∼4:1). Moreover, there is a striking
upregulation of toll-like receptor (TLR) 4 gene expression
within the brains of the same mice, and this expression is
primarily in microglia. Here we explored the impact of
gestational exposure to DEP or vehicle on microglial
morphology in the developing brains of male and female mice.
DEP exposure increased inflammatory cytokine protein and
altered the morphology of microglia, consistent with
activation or a delay in maturation, only within the
embryonic brains of male mice; and these effects were
dependent on TLR4. DEP exposure also increased cortical
volume at embryonic day (E)18, which switched to decreased
volume by post-natal day (P)30 in males, suggesting an
impact on the developing neural stem cell niche. Consistent
with this hypothesis, we found increased microglial-neuronal
interactions in male offspring that received DEP compared to
all other groups. Taken together, these data suggest a
mechanism by which prenatal exposure to environmental toxins
may affect microglial development and long-term function,
and thereby contribute to the risk of neurodevelopmental
disorders.},
Doi = {10.3389/fnsyn.2017.00010},
Key = {fds326607}
}
@article{fds290504,
Author = {Hanamsagar, R and Bilbo, SD},
Title = {Sex differences in neurodevelopmental and neurodegenerative
disorders: Focus on microglial function and
neuroinflammation during development.},
Journal = {The Journal of steroid biochemistry and molecular
biology},
Volume = {160},
Pages = {127-133},
Year = {2016},
Month = {June},
ISSN = {0960-0760},
url = {http://dx.doi.org/10.1016/j.jsbmb.2015.09.039},
Abstract = {Several neurological conditions are associated with sex
differences in prevalence or outcome. For example, autism
predominantly affects boys, depression is more common in
women, Parkinson's disease more common in men, and multiple
sclerosis in women. In the case of stroke, women have a less
favorable outcome and suffer from a more precipitous drop in
health status compared to men. As a result, treatment of
such diseases is difficult and yields variable results.
Despite this, sex is rarely considered when making treatment
decisions. The mechanisms underlying sex differences in
disease progression are not well understood, however a
strong link exists between different inflammation states of
men and women and their propensity to develop certain
diseases. As neuroinflammation is an important component of
pathophysiology in many neurological conditions, it can be
speculated that any changes in the state of inflammation in
the brain during normal development can potentially lead to
an increase in susceptibility to neurological and
neurodegenerative diseases. Microglia play a crucial role in
onset and modulation of inflammation and thus sex
differences in microglial function could explain, at least
in part, differences observed in susceptibilities and
outcomes of neurological disorders in men and women.
Understanding the mechanisms behind sex differences could
help develop more targeted therapy with higher success rate,
especially in diseases where sex differences are most
prominent.},
Doi = {10.1016/j.jsbmb.2015.09.039},
Key = {fds290504}
}
@article{fds321832,
Author = {Kraft, AD and Aschner, M and Cory-Slechta, DA and Bilbo, SD and Caudle,
WM and Makris, SL},
Title = {Unmasking silent neurotoxicity following developmental
exposure to environmental toxicants.},
Journal = {Neurotoxicology and teratology},
Volume = {55},
Pages = {38-44},
Year = {2016},
Month = {May},
url = {http://dx.doi.org/10.1016/j.ntt.2016.03.005},
Abstract = {Silent neurotoxicity, a term introduced approximately
25years ago, is defined as a persistent change to the
nervous system that does not manifest as overt evidence of
toxicity (i.e. it remains clinically unapparent) unless
unmasked by experimental or natural processes. Silent
neurotoxicants can be challenging for risk assessors, as the
multifactorial experiments needed to reveal their effects
are seldom conducted, and they are not addressed by current
study design guidelines. This topic was the focus of a
symposium addressing the interpretation and use of silent
neurotoxicity data in human health risk assessments of
environmental toxicants at the annual meeting of the
Developmental Neurotoxicology Society (previously the
Neurobehavioral Teratology Society) on June 30th, 2014.
Several factors important to the design and interpretation
of studies assessing the potential for silent neurotoxicity
were discussed by the panelists and audience members. Silent
neurotoxicity was demonstrated to be highly specific to the
characteristics of the animals being examined, the unmasking
agent tested, and the behavioral endpoint(s) evaluated.
Overall, the experimental examples presented highlighted a
need to consider common adverse outcomes and common
biological targets for chemical and non-chemical stressors,
particularly when the exposure and stressors are known to
co-occur. Risk assessors could improve the evaluation of
silent neurotoxicants in assessments through specific steps
from researchers, including experiments to reveal the
molecular targets and mechanisms that may result in specific
types of silent neurotoxicity, and experiments with complex
challenges reminiscent of the human situation.},
Doi = {10.1016/j.ntt.2016.03.005},
Key = {fds321832}
}
@article{fds250781,
Author = {Williamson, LL and McKenney, EA and Holzknecht, ZE and Belliveau, C and Rawls, JF and Poulton, S and Parker, W and Bilbo,
SD},
Title = {Got worms? Perinatal exposure to helminths prevents
persistent immune sensitization and cognitive dysfunction
induced by early-life infection.},
Journal = {Brain Behav Immun},
Volume = {51},
Pages = {14-28},
Year = {2016},
Month = {January},
ISSN = {0889-1591},
url = {http://dx.doi.org/10.1016/j.bbi.2015.07.006},
Abstract = {The incidence of autoimmune and inflammatory diseases has
risen dramatically in post-industrial societies. "Biome
depletion" - loss of commensal microbial and multicellular
organisms such as helminths (intestinal worms) that
profoundly modulate the immune system - may contribute to
these increases. Hyperimmune-associated disorders also
affect the brain, especially neurodevelopment, and
increasing evidence links early-life infection to cognitive
and neurodevelopmental disorders. We have demonstrated
previously that rats infected with bacteria as newborns
display life-long vulnerabilities to cognitive dysfunction,
a vulnerability that is specifically linked to long-term
hypersensitivity of microglial cell function, the resident
immune cells of the brain. Here, we demonstrate that
helminth colonization of pregnant dams attenuated the
exaggerated brain cytokine response of their offspring to
bacterial infection, and that combined with post-weaning
colonization of offspring with helminths (consistent with
their mothers treatment) completely prevented enduring
microglial sensitization and cognitive dysfunction in
adulthood. Importantly, helminths had no overt impact on
adaptive immune cell subsets, whereas exaggerated innate
inflammatory responses in splenic macrophages were
prevented. Finally, helminths altered the effect of neonatal
infection on the gut microbiome; neonatal infection with
Escherichia coli caused a shift from genera within the
Actinobacteria and Tenericutes phyla to genera in the
Bacteroidetes phylum in rats not colonized with helminths,
but helminths attenuated this effect. In sum, these data
point toward an inter-relatedness of various components of
the biome, and suggest potential mechanisms by which this
helminth might exert therapeutic benefits in the treatment
of neuroinflammatory and cognitive disorders.},
Doi = {10.1016/j.bbi.2015.07.006},
Key = {fds250781}
}
@article{fds321833,
Author = {Posillico, CK and Terasaki, LS and Bilbo, SD and Schwarz,
JM},
Title = {Examination of sex and minocycline treatment on acute
morphine-induced analgesia and inflammatory gene expression
along the pain pathway in Sprague-Dawley
rats.},
Journal = {Biology of sex differences},
Volume = {6},
Pages = {33},
Year = {2015},
Month = {January},
url = {http://dx.doi.org/10.1186/s13293-015-0049-3},
Abstract = {<h4>Background</h4>In addition to its classical effects on
opioid receptors, morphine can activate glia and stimulate
the production of pro-inflammatory immune molecules which in
turn counteract the analgesic properties of morphine. We
hypothesized that decreased morphine analgesia in females
may be the result of exaggerated microglial activation in
brain regions critical for analgesia.<h4>Methods</h4>Male
and female rats were treated with morphine and/or
minocycline and morphine analgesia was examined using the
hot plate. We also examined the expression of microglial and
astrocyte markers in the pain pathway.<h4>Results</h4>Males
treated with minocycline, a microglial inhibitor, exhibited
a significant increase in acute morphine analgesia as
previously shown; however, morphine analgesia was not
affected by minocycline pretreatment in female rats.
Minocycline decreased the expression of glial activation
markers in the male spinal cord and periaqueductal gray as
expected; however, these same molecules were upregulated in
the female.<h4>Conclusions</h4>These data describe a
significant difference between males and females in the
behavioral effects following co-administration of morphine
and minocycline.},
Doi = {10.1186/s13293-015-0049-3},
Key = {fds321833}
}
@article{fds250782,
Author = {McKenney, EA and Williamson, L and Yoder, AD and Rawls, JF and Bilbo,
SD and Parker, W},
Title = {Alteration of the rat cecal microbiome during colonization
with the helminth Hymenolepis diminuta.},
Journal = {Gut Microbes},
Volume = {6},
Number = {3},
Pages = {182-193},
Year = {2015},
ISSN = {1949-0976},
url = {http://dx.doi.org/10.1080/19490976.2015.1047128},
Abstract = {The microbiome is now widely recognized as being important
in health and disease, and makes up a substantial subset of
the biome within the ecosystem of the vertebrate body. At
the same time, multicellular, eukaryotic organisms such as
helminths are being recognized as an important component of
the biome that shaped the evolution of our genes. The
absence of these macroscopic organisms during the early
development and life of humans in Western culture probably
leads to a wide range of human immunological diseases.
However, the interaction between the microbiome and
macroscopic components of the biome remains poorly
characterized. In this study, the microbiome of the cecum in
rats colonized for 2 generations with the small intestinal
helminth Hymenolepis diminuta was evaluated. The
introduction of this benign helminth, which is of
considerable therapeutic interest, led to several changes in
the cecal microbiome. Most of the changes were within the
Firmicutes phylum, involved about 20% of the total bacteria,
and generally entailed a shift from Bacilli to Clostridia
species in the presence of the helminth. The results point
toward ecological relationships between various components
of the biome, with the observed shifts in the microbiome
suggesting potential mechanisms by which this helminth might
exert therapeutic effects.},
Doi = {10.1080/19490976.2015.1047128},
Key = {fds250782}
}
@article{fds250783,
Author = {Bilbo, SD and Nevison, CD and Parker, W},
Title = {A model for the induction of autism in the ecosystem of the
human body: the anatomy of a modern pandemic?},
Journal = {Microb Ecol Health Dis},
Volume = {26},
Pages = {26253},
Year = {2015},
ISSN = {0891-060X},
url = {http://dx.doi.org/10.3402/mehd.v26.26253},
Abstract = {BACKGROUND: The field of autism research is currently
divided based on a fundamental question regarding the nature
of autism: Some are convinced that autism is a pandemic of
modern culture, with environmental factors at the roots.
Others are convinced that the disease is not pandemic in
nature, but rather that it has been with humanity for
millennia, with its biological and neurological
underpinnings just now being understood. OBJECTIVE: In this
review, two lines of reasoning are examined which suggest
that autism is indeed a pandemic of modern culture. First,
given the widely appreciated derailment of immune function
by modern culture, evidence that autism is strongly
associated with aberrant immune function is examined.
Second, evidence is reviewed indicating that autism is
associated with 'triggers' that are, for the most part, a
construct of modern culture. In light of this reasoning,
current epidemiological evidence regarding the incidence of
autism, including the role of changing awareness and
diagnostic criteria, is examined. Finally, the potential
role of the microbial flora (the microbiome) in the
pathogenesis of autism is discussed, with the view that the
microbial flora is a subset of the life associated with the
human body, and that the entire human biome, including both
the microbial flora and the fauna, has been radically
destabilized by modern culture. CONCLUSIONS: It is suggested
that the unequivocal way to resolve the debate regarding the
pandemic nature of autism is to perform an experiment:
monitor the prevalence of autism after normalizing immune
function in a Western population using readily available
approaches that address the well-known factors underlying
the immune dysfunction in that population.},
Doi = {10.3402/mehd.v26.26253},
Key = {fds250783}
}
@article{fds250784,
Author = {Bolton, JL and Bilbo, SD},
Title = {Developmental programming of brain and behavior by perinatal
diet: focus on inflammatory mechanisms.},
Journal = {Dialogues in clinical neuroscience},
Volume = {16},
Number = {3},
Pages = {307-320},
Year = {2014},
Month = {September},
ISSN = {1294-8322},
Abstract = {Obesity is now epidemic worldwide. Beyond associated
diseases such as diabetes, obesity is linked to
neuropsychiatric disorders such as depression. Alarmingly
maternal obesity and high-fat diet consumption during
gestation/lactation may "program" offspring longterm for
increased obesity themselves, along with increased
vulnerability to mood disorders. We review the evidence that
programming of brain and behavior by perinatal diet is
propagated by inflammatory mechanisms, as obesity and
high-fat diets are independently associated with exaggerated
systemic levels of inflammatory mediators. Due to the
recognized dual role of these immune molecules (eg,
interleukin [IL]-6, 11-1β) in placental function and brain
development, any disruption of their delicate balance with
growth factors or neurotransmitters (eg, serotonin) by
inflammation early in life can permanently alter the
trajectory of fetal brain development. Finally, epigenetic
regulation of inflammatory pathways is a likely candidate
for persistent changes in metabolic and brain function as a
consequence of the perinatal environment.},
Key = {fds250784}
}
@article{fds250789,
Author = {Williamson, LL and Bilbo, SD},
Title = {Neonatal infection modulates behavioral flexibility and
hippocampal activation on a Morris Water Maze
task.},
Journal = {Physiology & behavior},
Volume = {129},
Pages = {152-159},
Year = {2014},
Month = {April},
ISSN = {0031-9384},
url = {http://dx.doi.org/10.1016/j.physbeh.2014.02.033},
Abstract = {Neonatal infection has enduring effects on the brain, both
at the cellular and behavioral levels. We determined the
effects of peripheral infection with Escherichia coli at
postnatal day (P) 4 in rats on a water maze task in
adulthood, and assessed neuronal activation in the dentate
gyrus (DG) following the memory test. Rats were trained and
tested on one of 3 distinct water maze task paradigms: 1)
minimal training (18 trials/3days), 2) extended training (50
trials/10days) or 3) reversal training (extended training
followed by 30 trials/3days with a new platform location).
Following a 48h memory test, brains were harvested to assess
neuronal activation using activity-regulated
cytoskeleton-associated (Arc) protein in the DG. Following
minimal training, rats treated neonatally with E. coli had
improved performance and paradoxically reduced Arc
expression during the memory test compared to control rats
treated with PBS early in life. However, neonatally-infected
rats did not differ from control rats in behavior or
neuronal activation during the memory test following
extended training. Furthermore, rats treated neonatally with
E. coli were significantly impaired during the 48h memory
test for a reversal platform location, unlike controls.
Specifically, whereas neonatally-infected rats were able to
acquire the new location at the same rate as controls, they
spent significantly less time in the target quadrant for the
reversal platform during a memory test. However,
neonatally-infected and control rats had similar levels of
Arc expression following the 48h memory test for reversal.
Together, these data indicate that neonatal infection may
improve the rate of acquisition on hippocampal-dependent
tasks while impairing flexibility on the same tasks; in
addition, network activation in the DG during learning may
be predictive of future cognitive flexibility on a
hippocampal-dependent task.},
Doi = {10.1016/j.physbeh.2014.02.033},
Key = {fds250789}
}
@article{fds250791,
Author = {Bolton, JL and Auten, RL and Bilbo, SD},
Title = {Prenatal air pollution exposure induces sexually dimorphic
fetal programming of metabolic and neuroinflammatory
outcomes in adult offspring.},
Journal = {Brain, behavior, and immunity},
Volume = {37},
Pages = {30-44},
Year = {2014},
Month = {March},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24184474},
Abstract = {Environmental chemical exposures during critical windows of
development may contribute to the escalating prevalence of
obesity. We tested the hypothesis that prenatal exposure to
diesel exhaust particles (DEP), a primary component of air
pollution, would prime microglia long-term, resulting in
exacerbated metabolic and affective outcomes following
exposure to a high-fat diet in adulthood. Time-mated mouse
dams were intermittently exposed to respiratory
instillations of either vehicle (VEH) or DEP throughout
gestation. Adult male and female offspring were then fed
either a low-fat diet (LFD) or high-fat diet (HFD) for 9
weeks. The male offspring of DEP-exposed dams exhibited
exaggerated weight gain, insulin resistance, and
anxiety-like behavior on HFD compared to the male offspring
of VEH-exposed dams, whereas female offspring did not differ
according to prenatal treatment. Furthermore, HFD induced
evidence of macrophage infiltration of both adipose tissue
and the brain in both sexes, but these cells were more
activated specifically in DEP/HFD males. DEP/HFD males also
expressed markedly higher levels of microglial/macrophage,
but not astrocyte, activation markers in the hippocampus,
whereas females exhibited only a suppression of astrocyte
activation markers due to HFD. In a second experiment, DEP
male offspring mounted an exaggerated peripheral IL-1β
response to an LPS challenge at postnatal day (P)30, whereas
their central IL-1β response did not differ from VEH male
offspring, which is suggestive of macrophage priming due to
prenatal DEP exposure. In sum, prenatal air pollution
exposure "programs" offspring for increased susceptibility
to diet-induced metabolic, behavioral, and neuroinflammatory
changes in adulthood in a sexually dimorphic
manner.},
Doi = {10.1016/j.bbi.2013.10.029},
Key = {fds250791}
}
@article{fds250786,
Author = {Bilbo, SD and Williamson, LL and Parker, W},
Title = {Early-Life Programming of Neuroendocrine Function by the
Immune System: Plasticity or Autoimmunity due to Biome
Depletion?},
Journal = {INTEGRATIVE AND COMPARATIVE BIOLOGY},
Volume = {54},
Pages = {E19-E19},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2014},
Month = {January},
ISSN = {1540-7063},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000333049500074&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds250786}
}
@article{fds250785,
Author = {Bolton, JL and Smith, SH and Huff, NC and Ian Gilmour and M and Michael
Foster, W and Auten, RL and Bilbo, SD},
Title = {Erratum: Prenatal air pollution exposure induces
neuroinflammation and predisposes offspring to weight gain
in adulthood in a sex-specific manner (FASEB Journal (2012)
26 (4743-4754) DOI:10.1096/fj.12-210989)},
Journal = {FASEB Journal},
Volume = {28},
Number = {6},
Pages = {2737-2738},
Year = {2014},
Month = {January},
ISSN = {0892-6638},
url = {http://dx.doi.org/10.1096/fj.12-210989ERR},
Doi = {10.1096/fj.12-210989ERR},
Key = {fds250785}
}
@article{fds250788,
Author = {Bolton, JL and Auten, RL and Bilbo, SD},
Title = {Prenatal air pollution exposure induces sexually dimorphic
fetal programming of metabolic and neuroinflammatory
outcomes in adult offspring},
Journal = {Brain, Behavior, and Immunity},
Volume = {37},
Pages = {30-44},
Year = {2014},
ISSN = {0889-1591},
url = {http://dx.doi.org/10.1016/j.bbi.2013.10.029},
Keywords = {Adipose tissue • Anxiety • Diesel exhaust
particles • Fetal programming • High-fat diet
• Hippocampus • Hypothalamus • Insulin
resistance • Macrophages • Microglia},
Abstract = {HASH(0xcfc2fa8)},
Language = {ENG},
Doi = {10.1016/j.bbi.2013.10.029},
Key = {fds250788}
}
@article{fds250795,
Author = {Schwarz, JM and Smith, SH and Bilbo, SD},
Title = {FACS analysis of neuronal-glial interactions in the nucleus
accumbens following morphine administration.},
Journal = {Psychopharmacology},
Volume = {230},
Number = {4},
Pages = {525-535},
Year = {2013},
Month = {December},
ISSN = {0033-3158},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23793269},
Abstract = {<h4>Rationale</h4>Glia, including astrocytes and microglia,
can profoundly modulate neuronal function and behavior;
however, very little is known about the signaling molecules
that govern neuronal-glial communication and in turn affect
behavior. Morphine treatment activates microglia and
astrocytes in the nucleus accumbens (NAcc) to induce the
synthesis of cytokines and chemokines, and this has
important implications for addictive behavior. Blocking
morphine-induced glial activation using the nonspecific
glial inhibitor, ibudilast, has no effect on the initial
rewarding properties of morphine, but completely prevents
the relapse of drug-seeking behavior months
later.<h4>Objectives</h4>We sought to determine the cellular
source of these cytokines and chemokines in the NAcc in
response to morphine, and the cell-type-specific expression
pattern of their receptors to determine whether neurons have
the capacity to respond to these immune signals
directly.<h4>Methods</h4>We used fluorescence-activated cell
sorting of neurons (Thy1+), astrocytes (GLT1+), and
microglia (CD11b+) from the NAcc for the analysis of cell
type specific gene expression following morphine or saline
treatment.<h4>Results</h4>The results indicate that
microglia and neurons each produce a subset of chemokines in
response to morphine and that neurons have the capacity to
respond directly to a select group of these chemokines via
their receptors. In addition, we provide evidence that
microglia are capable of responding directly to dopamine
release in the NAcc.<h4>Conclusions</h4>Future studies will
examine the mechanism(s) by which neurons respond to these
immune signals produced by microglia in an effort to
understand their effect on addictive behaviors.},
Language = {eng},
Doi = {10.1007/s00213-013-3180-z},
Key = {fds250795}
}
@article{fds250792,
Author = {Lieblein-Boff, JC and McKim, DB and Shea, DT and Wei, P and Deng, Z and Sawicki, C and Quan, N and Bilbo, SD and Bailey, MT and McTigue, DM and Godbout, JP},
Title = {Neonatal E. coli infection causes neuro-behavioral deficits
associated with hypomyelination and neuronal sequestration
of iron.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {33},
Number = {41},
Pages = {16334-16345},
Year = {2013},
Month = {October},
ISSN = {1529-2401},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24107964},
Abstract = {Recent evidence indicates that inflammatory insults in
neonates significantly influenced white matter development
and caused behavioral deficits that manifest in young
adulthood. The mechanisms underlying these developmental and
behavioral complications, however, are not well understood.
We hypothesize that acute brain inflammation caused by
neonatal infection reduces the bioavailability of iron
required for oligodendrocyte maturation and white matter
development. Here, we confirm that peripheral Escherichia
coli infection in neonates at postnatal day 3 (P3) caused
acute brain inflammation that was resolved within 72 h.
Nonetheless, transient early life infection (ELI) profoundly
influenced behavior, white matter development, and iron
homeostasis in the brain. For instance, mice exposed to E.
coli as neonates had increased locomotor activity and
impaired motor coordination as juveniles (P35) and young
adults (P60). In addition, these behavioral deficits were
associated with marked hypomyelination and a reduction of
oligodendrocytes in subcortical white matter and motor
cortex. Moreover, ELI altered transcripts related to
cellular sequestration of iron in the brain including
hepcidin, ferroportin, and L-ferritin. For example, ELI
increased hepcidin mRNA and decreased ferroportin mRNA and
protein in the brain at P4, which preceded increased
L-ferritin mRNA at P12. Consistent with the mRNA results,
L-ferritin protein was robustly increased at P12
specifically in neurons of E. coli infected mice. We
interpret these data to indicate that neonatal infection
causes significant neuronal sequestration of iron at a time
point before myelination. Together, these data indicate a
possible role for aberrant neuronal iron storage in neonatal
infection-induced disturbances in myelination and
behavior.},
Language = {eng},
Doi = {10.1523/jneurosci.0708-13.2013},
Key = {fds250792}
}
@article{fds250793,
Author = {Bolton, JL and Huff, NC and Smith, SH and Mason, SN and Foster, WM and Auten, RL and Bilbo, SD},
Title = {Maternal stress and effects of prenatal air pollution on
offspring mental health outcomes in mice.},
Journal = {Environmental health perspectives},
Volume = {121},
Number = {9},
Pages = {1075-1082},
Year = {2013},
Month = {September},
ISSN = {1552-9924},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23823752},
Abstract = {<h4>Background</h4>Low socioeconomic status is consistently
associated with reduced physical and mental health, but the
mechanisms remain unclear. Increased levels of urban air
pollutants interacting with parental stress have been
proposed to explain health disparities in respiratory
disease, but the impact of such interactions on mental
health is unknown.<h4>Objectives</h4>We aimed to determine
whether prenatal air pollution exposure and stress during
pregnancy act synergistically on offspring to induce a
neuroinflammatory response and subsequent neurocognitive
disorders in adulthood.<h4>Methods</h4>Mouse dams were
intermittently exposed via oropharyngeal aspiration to
diesel exhaust particles (DEP; 50 μg × 6 doses) or vehicle
throughout gestation. This exposure was combined with
standard housing or nest material restriction (NR; a novel
model of maternal stress) during the last third of
gestation.<h4>Results</h4>Adult (postnatal day 60) offspring
of dams that experienced both stressors (DEP and NR)
displayed increased anxiety, but only male offspring of this
group had impaired cognition. Furthermore, maternal DEP
exposure increased proinflammatory interleukin (IL)-1β
levels within the brains of adult males but not females, and
maternal DEP and NR both decreased anti-inflammatory IL-10
in male, but not female, brains. Similarly, only DEP/NR
males showed increased expression of the innate immune
recognition gene toll-like receptor 4 (Tlr4) and its
downstream effector, caspase-1.<h4>Conclusions</h4>These
results show that maternal stress during late gestation
increases the susceptibility of offspring-particularly
males-to the deleterious effects of prenatal air pollutant
exposure, which may be due to a synergism of these factors
acting on innate immune recognition genes and downstream
neuroinflammatory cascades within the developing
brain.},
Language = {eng},
Doi = {10.1289/ehp.1306560},
Key = {fds250793}
}
@article{fds250796,
Author = {Bilbo, SD},
Title = {Frank A. Beach award: programming of neuroendocrine function
by early-life experience: a critical role for the immune
system.},
Journal = {Hormones and behavior},
Volume = {63},
Number = {5},
Pages = {684-691},
Year = {2013},
Month = {May},
ISSN = {1095-6867},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23474365},
Abstract = {Many neuropsychiatric disorders are associated with a strong
dysregulation of the immune system, and several have a
striking etiology in development as well. Our recent
evidence using a rodent model of neonatal Escherichia coli
infection has revealed novel insight into the mechanisms
underlying cognitive deficits in adulthood, and suggests
that the early-life immune history of an individual may be
critical to understanding the relative risk of developing
later-life mental health disorders in humans. A single
neonatal infection programs the function of immune cells
within the brain, called microglia, for the life of the
rodent such that an adult immune challenge results in
exaggerated cytokine production within the brain and
associated cognitive deficits. I describe the important role
of the immune system, notably microglia, during brain
development, and discuss some of the many ways in which
immune activation during early brain development can affect
the later-life outcomes of neural function, immune function,
and cognition.},
Language = {eng},
Doi = {10.1016/j.yhbeh.2013.02.017},
Key = {fds250796}
}
@article{fds250797,
Author = {Williamson, LL and Bilbo, SD},
Title = {Chemokines and the hippocampus: a new perspective on
hippocampal plasticity and vulnerability.},
Journal = {Brain, behavior, and immunity},
Volume = {30},
Pages = {186-194},
Year = {2013},
Month = {May},
ISSN = {0889-1591},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23376170},
Keywords = {Animals • Chemokines • Conditioning (Psychology)
• Cytokines • Hippocampus • Learning •
Memory • Neurogenesis • Neuronal Plasticity •
Neurons • metabolism* • physiology •
physiology*},
Abstract = {The hippocampus is critical for several aspects of learning
and memory and is unique among other cortical regions in
structure, function and the potential for plasticity. This
remarkable region recapitulates development throughout the
lifespan with enduring neurogenesis and well-characterized
plasticity. The structure and traits of the hippocampus that
distinguish it from other brain regions, however, may be the
same reasons that this important brain region is
particularly vulnerable to insult and injury. The immune
system within the brain responds to insult and injury, and
the hippocampus and the immune system are extensively
interconnected. Immune signaling molecules, cytokines and
chemokines (chemotactic cytokines), are well known for their
functions during insult or injury. They are also
increasingly implicated in normal hippocampal neurogenesis
(e.g., CXCR4 on newborn neurons), cellular plasticity (e.g.,
interleukin-6 in LTP maintenance), and learning and memory
(e.g., interleukin-1β in fear conditioning). We provide
evidence from the small but growing literature that
neuroimmune interactions and immune signaling molecules,
especially chemokines, may be a primary underlying mechanism
for the coexistence of plasticity and vulnerability within
the hippocampus. We also highlight the evidence that the
hippocampus exhibits a remarkable resilience in response to
diverse environmental events (e.g., enrichment, exercise),
which all may converge onto common neuroimmune
mechanisms.},
Language = {eng},
Doi = {10.1016/j.bbi.2013.01.077},
Key = {fds250797}
}
@article{fds250824,
Author = {Schwarz, JM and Bilbo, SD},
Title = {Adolescent morphine exposure affects long-term microglial
function and later-life relapse liability in a model of
addiction.},
Journal = {J Neurosci},
Volume = {33},
Number = {3},
Pages = {961-971},
Year = {2013},
Month = {January},
ISSN = {1529-2401},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23325235},
Keywords = {Age Factors • Animals • Conditioning, Operant
• Disease Models, Animal • Drug-Seeking Behavior
• Microglia • Minocycline • Morphine •
Narcotics • Nucleus Accumbens • Opioid-Related
Disorders • Pyridines • Rats • Rats,
Sprague-Dawley • Recurrence • Toll-Like Receptor 4
• drug effects • drug effects* • genetics
• immunology • immunology* • metabolism
• pharmacology • pharmacology* •
physiology},
Abstract = {Adolescence in humans represents a unique developmental time
point associated with increased risk-taking behavior and
experimentation with drugs of abuse. We hypothesized that
exposure to drugs of abuse during adolescence may increase
the risk of addiction in adulthood. To test this, rats were
treated with a subchronic regimen of morphine or saline in
adolescence, and their preference for morphine was examined
using conditioned place preference (CPP) and drug-induced
reinstatement in adulthood. The initial preference for
morphine did not differ between groups; however, rats
treated with morphine during adolescence showed robust
reinstatement of morphine CPP after drug re-exposure in
adulthood. This effect was not seen in rats pretreated with
a subchronic regimen of morphine as adults, suggesting that
exposure to morphine specifically during adolescence
increases the risk of relapse to drug-seeking behavior in
adulthood. We have previously established a role for
microglia, the immune cells of the brain, and immune
molecules in the risk of drug-induced reinstatement of
morphine CPP. Thus, we examined the role of microglia within
the nucleus accumbens of these rats and determined that rats
exposed to morphine during adolescence had a significant
increase in Toll-like receptor 4 (TLR4) mRNA and protein
expression specifically on microglia. Morphine binds to TLR4
directly, and this increase in TLR4 was associated with
exaggerated morphine-induced TLR4 signaling and microglial
activation in rats previously exposed to morphine during
adolescence. These data suggest that long-term changes in
microglial function, caused by adolescent morphine exposure,
alter the risk of drug-induced reinstatement in
adulthood.},
Language = {eng},
Doi = {10.1523/JNEUROSCI.2516-12.2013},
Key = {fds250824}
}
@article{fds250829,
Author = {Block, ML and Elder, A and Auten, RL and Bilbo, SD and Chen, H and Chen,
JC and Cory Slechta and DA and Costa, D and Diaz Sanchez and D and Dorman, DC and Gold, DR and Gray, K and Jeng, HA and Kaufman, JD and Kleinman, MT and Kirshner, A and Lawler, C and Miller, DS and Nadadur, SS and Ritz, B and Semmens, EO and Tonelli, LH and Veronesi, B and Wright, RO and Wright,
RJ},
Title = {The outdoor air pollution and brain health
workshop.},
Journal = {Neurotoxicology},
Volume = {33},
Number = {5},
Pages = {972-984},
Year = {2012},
Month = {October},
ISSN = {1872-9711},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22981845},
Abstract = {Accumulating evidence suggests that outdoor air pollution
may have a significant impact on central nervous system
(CNS) health and disease. To address this issue, the
National Institute of Environmental Health Sciences/National
Institute of Health convened a panel of research scientists
that was assigned the task of identifying research gaps and
priority goals essential for advancing this growing field
and addressing an emerging human health concern. Here, we
review recent findings that have established the effects of
inhaled air pollutants in the brain, explore the potential
mechanisms driving these phenomena, and discuss the
recommended research priorities/approaches that were
identified by the panel.},
Language = {eng},
Doi = {10.1016/j.neuro.2012.08.014},
Key = {fds250829}
}
@article{fds250818,
Author = {Bilbo, SD and Klein, SL},
Title = {Special Issue: the neuroendocrine-immune axis in health and
disease.},
Journal = {Hormones and behavior},
Volume = {62},
Number = {3},
Pages = {187-190},
Year = {2012},
Month = {August},
ISSN = {1095-6867},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22789778},
Language = {eng},
Doi = {10.1016/j.yhbeh.2012.06.005},
Key = {fds250818}
}
@article{fds250819,
Author = {Bilbo, SD and Schwarz, JM},
Title = {The immune system and developmental programming of brain and
behavior.},
Journal = {Front Neuroendocrinol},
Volume = {33},
Number = {3},
Pages = {267-286},
Year = {2012},
Month = {August},
ISSN = {1095-6808},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22982535},
Abstract = {The brain, endocrine, and immune systems are inextricably
linked. Immune molecules have a powerful impact on
neuroendocrine function, including hormone-behavior
interactions, during health as well as sickness. Similarly,
alterations in hormones, such as during stress, can
powerfully impact immune function or reactivity. These
functional shifts are evolved, adaptive responses that
organize changes in behavior and mobilize immune resources,
but can also lead to pathology or exacerbate disease if
prolonged or exaggerated. The developing brain in particular
is exquisitely sensitive to both endogenous and exogenous
signals, and increasing evidence suggests the immune system
has a critical role in brain development and associated
behavioral outcomes for the life of the individual. Indeed,
there are associations between many neuropsychiatric
disorders and immune dysfunction, with a distinct etiology
in neurodevelopment. The goal of this review is to describe
the important role of the immune system during brain
development, and to discuss some of the many ways in which
immune activation during early brain development can affect
the later-life outcomes of neural function, immune function,
mood and cognition.},
Language = {eng},
Doi = {10.1016/j.yfrne.2012.08.006},
Key = {fds250819}
}
@article{fds250831,
Author = {Schwarz, JM and Bilbo, SD},
Title = {Sex, glia, and development: interactions in health and
disease.},
Journal = {Horm Behav},
Volume = {62},
Number = {3},
Pages = {243-253},
Year = {2012},
Month = {August},
ISSN = {1095-6867},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22387107},
Abstract = {Microglia and astrocytes are the primary immune cells within
the central nervous system. Microglia influence processes
including neural development, synaptic plasticity and
cognition; while their activation and production of immune
molecules can induce stereotyped sickness behaviors or
pathologies including cognitive dysfunction. Given their
role in health and disease, we propose that glia may also be
a critical link in understanding the etiology of many
neuropsychiatric disorders that present with a strong
sex-bias in their symptoms or prevalence. Specifically,
males are more likely to be diagnosed with disorders that
have distinct developmental origins such as autism or
schizophrenia. In contrast, females are more likely to be
diagnosed with disorders that present later in life, after
the onset of adolescence, such as depression and anxiety
disorders. In this review we will summarize the evidence
suggesting that sex differences in the colonization and
function of glia within the normal developing brain may
contribute to distinct windows of vulnerability between
males and females. We will also highlight the current gaps
in our knowledge as well as the future directions and
considerations of research aimed at understanding the link
between neuroimmune function and sex differences in mental
health disorders.},
Language = {eng},
Doi = {10.1016/j.yhbeh.2012.02.018},
Key = {fds250831}
}
@article{fds250830,
Author = {Bolton, JL and Smith, SH and Huff, NC and Gilmour, MI and Foster, WM and Auten, RL and Bilbo, SD},
Title = {Prenatal air pollution exposure induces neuroinflammation
and predisposes offspring to weight gain in adulthood in a
sex-specific manner.},
Journal = {FASEB journal : official publication of the Federation of
American Societies for Experimental Biology},
Volume = {26},
Number = {11},
Pages = {4743-4754},
Year = {2012},
Month = {July},
ISSN = {1530-6860},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22815382},
Abstract = {Emerging evidence suggests environmental chemical exposures
during critical windows of development may contribute to the
escalating prevalence of obesity. We tested the hypothesis
that prenatal air pollution exposure would predispose the
offspring to weight gain in adulthood. Pregnant mice were
exposed to filtered air (FA) or diesel exhaust (DE) on
embryonic days (E) 9-17. Prenatal DE induced a significant
fetal brain cytokine response at E18 (46-390% over FA). As
adults, offspring were fed either a low-fat diet (LFD) or
high-fat diet (HFD) for 6 wk. Adult DE male offspring
weighed 12% more and were 35% less active than FA male
offspring at baseline, whereas there were no differences in
females. Following HFD, DE males gained weight at the same
rate as FA males, whereas DE females gained 340% more weight
than FA females. DE-HFD males had 450% higher endpoint
insulin levels than FA-HFD males, and all males on HFD
showed decreased activity and increased anxiety, whereas
females showed no differences. Finally, both DE males and
females fed HFD showed increased microglial activation
(30-66%) within several brain regions. Thus, prenatal air
pollution exposure can "program" offspring for increased
susceptibility to diet-induced weight gain and
neuroinflammation in adulthood in a sex-specific
manner.-Bolton, J. L., Smith, S. H., Huff, N. C., Gilmour,
M. I., Foster, W. M., Auten, R. L., Bilbo, S. D. Prenatal
air pollution exposure induces neuroinflammation and
predisposes offspring to weight gain in adulthood in a
sex-specific manner.},
Language = {eng},
Doi = {10.1096/fj.12-210989},
Key = {fds250830}
}
@article{fds250800,
Author = {Bilbo, SD},
Title = {Sex Differences in Early-Life Programming of
Neuroinflammation and Behavioral Abnormalities by High Fat
Diet},
Journal = {BIOLOGICAL PSYCHIATRY},
Volume = {71},
Number = {8},
Pages = {12S-12S},
Publisher = {ELSEVIER SCIENCE INC},
Year = {2012},
Month = {April},
ISSN = {0006-3223},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000302466000040&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds250800}
}
@article{fds250820,
Author = {Schwarz, JM and Sholar, PW and Bilbo, SD},
Title = {Sex differences in microglial colonization of the developing
rat brain.},
Journal = {Journal of neurochemistry},
Volume = {120},
Number = {6},
Pages = {948-963},
Year = {2012},
Month = {March},
ISSN = {1471-4159},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22182318},
Keywords = {Age Factors • Animals • Animals, Newborn •
Brain • Calcium-Binding Proteins • Cell Count
• Chemokine CXCL9 • Embryo, Mammalian •
Enzyme-Linked Immunosorbent Assay • Female • Flow
Cytometry • Gene Expression Regulation, Developmental
• Interleukin-10 • Interleukin-1beta • Male
• Microfilament Proteins • Microglia • RNA,
Messenger • Rats • Rats, Sprague-Dawley • Sex
Characteristics* • cytology* • genetics •
growth & development* • metabolism •
physiology*},
Abstract = {Microglia are the resident immune cells within the brain and
their production of immune molecules such as cytokines and
chemokines is critical for the processes of normal brain
development including neurogenesis, axonal migration,
synapse formation, and programmed cell death. Notably, sex
differences exist in many of these processes throughout
brain development; however, it is unknown whether a sex
difference concurrently exists in the colonization, number,
or morphology of microglia within the developing brain. We
demonstrate for the first time that the number and
morphology of microglia throughout development is dependent
upon the sex and age of the individual, as well as the brain
region of interest. Males have overall more microglia early
in postnatal development [postnatal day (P) 4], whereas
females have more microglia with an activated/amoeboid
morphology later in development, as juveniles and adults
(P30-60). Finally, gene expression of a large number of
cytokines, chemokines and their receptors shifts
dramatically over development, and is highly dependent upon
sex. Taken together, these data warrant further research
into the role that sex-dependent mechanisms may play in
microglial colonization, number, and function, and their
potential contribution to neural development, function, or
potential dysfunction.},
Language = {eng},
Doi = {10.1111/j.1471-4159.2011.07630.x},
Key = {fds250820}
}
@article{fds250821,
Author = {Williamson, LL and Chao, A and Bilbo, SD},
Title = {Environmental enrichment alters glial antigen expression and
neuroimmune function in the adult rat hippocampus.},
Journal = {Brain, behavior, and immunity},
Volume = {26},
Number = {3},
Pages = {500-510},
Year = {2012},
Month = {March},
ISSN = {1090-2139},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22281279},
Keywords = {Animals • Astrocytes • Brain-Derived Neurotrophic
Factor • Calcium-Binding Proteins • Chemokines
• Corticosterone • Cytokines • Dentate Gyrus
• Environment* • Gene Expression • Glial
Fibrillary Acidic Protein • Hippocampus •
Inflammation Mediators • Lipopolysaccharides •
Male • Microfilament Proteins • Microglia •
Neurogenesis* • Rats • Rats, Sprague-Dawley •
immunology • immunology* • metabolism},
Abstract = {Neurogenesis is a well-characterized phenomenon within the
dentate gyrus (DG) of the adult hippocampus. Environmental
enrichment (EE) in rodents increases neurogenesis, enhances
cognition, and promotes recovery from injury. However,
little is known about the effects of EE on glia (astrocytes
and microglia). Given their importance in neural repair, we
predicted that EE would modulate glial phenotype and/or
function within the hippocampus. Adult male rats were housed
either 12 h/day in an enriched environment or in a standard
home cage. Rats were injected with BrdU at 1 week, and after
7 weeks, half of the rats from each housing group were
injected with lipopolysaccharide (LPS), and cytokine and
chemokine expression was assessed within the periphery,
hippocampus and cortex. Enriched rats had a markedly blunted
pro-inflammatory response to LPS within the hippocampus.
Specifically, expression of the chemokines Ccl2, Ccl3 and
Cxcl2, several members of the tumor necrosis factor (TNF)
family, and the pro-inflammatory cytokine IL-1β were all
significantly decreased following LPS administration in EE
rats compared to controls. EE did not impact the
inflammatory response to LPS in the cortex. Moreover, EE
significantly increased both astrocyte (GFAP+) and microglia
(Iba1+) antigen expression within the DG, but not in the
CA1, CA3, or cortex. Measures of neurogenesis were not
impacted by EE (BrdU and DCX staining), although hippocampal
BDNF mRNA was significantly increased by EE. This study
demonstrates the importance of environmental factors on the
function of the immune system specifically within the brain,
which can have profound effects on neural
function.},
Language = {eng},
Doi = {10.1016/j.bbi.2012.01.003},
Key = {fds250821}
}
@article{fds250825,
Author = {Bilbo, SD and Jones, JP and Parker, W},
Title = {Is autism a member of a family of diseases resulting from
genetic/cultural mismatches? Implications for treatment and
prevention.},
Journal = {Autism Res Treat},
Volume = {2012},
Pages = {910946},
Year = {2012},
ISSN = {2090-1933},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22928103},
Abstract = {Several lines of evidence support the view that autism is a
typical member of a large family of immune-related,
noninfectious, chronic diseases associated with
postindustrial society. This family of diseases includes a
wide range of inflammatory, allergic, and autoimmune
diseases and results from consequences of genetic/culture
mismatches which profoundly destabilize the immune system.
Principle among these consequences is depletion of important
components, particularly helminths, from the ecosystem of
the human body, the human biome. Autism shares a wide range
of features in common with this family of diseases,
including the contribution of genetics/epigenetics, the
identification of disease-inducing triggers, the apparent
role of immunity in pathogenesis, high prevalence, complex
etiologies and manifestations, and potentially some aspects
of epidemiology. Fortunately, using available resources and
technology, modern medicine has the potential to effectively
reconstitute the human biome, thus treating or even avoiding
altogether the consequences of genetic/cultural mismatches
which underpin this entire family of disease. Thus, if
indeed autism is an epidemic of postindustrial society
associated with immune hypersensitivity, we can expect that
the disease is readily preventable.},
Language = {eng},
Doi = {10.1155/2012/910946},
Key = {fds250825}
}
@article{fds250826,
Author = {Bolton, JL and Huff, NC and Smith, SH and Potts Kant and EN and Mason, SN and Auten, RL and Bilbo, SD},
Title = {Synergism in Fetal Programming: The Combined Effects of
Prenatal Air Pollution & Stress Exposures on Offspring
Neuroimmune Function & Behavior},
Journal = {Molecular Psychiatry},
Year = {2012},
Key = {fds250826}
}
@article{fds250827,
Author = {Williamson, LL and Bilbo, SD},
Title = {The plasticity of the hippocampus is the reason for its
vulnerability: Neuroimmune interactions and their role in
the hippocampus},
Journal = {Brain, Behavior, and Immunity},
Year = {2012},
Key = {fds250827}
}
@article{fds250828,
Author = {Schwarz, JM and Smith, SH and Bilbo, SD},
Title = {Neuronal-glial interactions in the nucleus accumbens
following morphine.},
Journal = {Glia},
Year = {2012},
Key = {fds250828}
}
@article{fds250832,
Author = {Schwarz, JM and Hutchinson, MR and Bilbo, SD},
Title = {Early-life experience decreases drug-induced reinstatement
of morphine CPP in adulthood via microglial-specific
epigenetic programming of anti-inflammatory IL-10
expression.},
Journal = {J Neurosci},
Volume = {31},
Number = {49},
Pages = {17835-17847},
Year = {2011},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22159099},
Abstract = {A critical component of drug addiction research involves
identifying novel biological mechanisms and environmental
predictors of risk or resilience to drug addiction and
associated relapse. Increasing evidence suggests microglia
and astrocytes can profoundly affect the physiological and
addictive properties of drugs of abuse, including morphine.
We report that glia within the rat nucleus accumbens (NAcc)
respond to morphine with an increase in cytokine/chemokine
expression, which predicts future reinstatement of morphine
conditioned place preference (CPP) following a priming dose
of morphine. This glial response to morphine is influenced
by early-life experience. A neonatal handling paradigm that
increases the quantity and quality of maternal care
significantly increases baseline expression of the
anti-inflammatory cytokine IL-10 within the NAcc, attenuates
morphine-induced glial activation, and prevents the
subsequent reinstatement of morphine CPP in adulthood. IL-10
expression within the NAcc and reinstatement of CPP are
negatively correlated, suggesting a protective role for this
specific cytokine against morphine-induced glial reactivity
and drug-induced reinstatement of morphine CPP. Neonatal
handling programs the expression of IL-10 within the NAcc
early in development, and this is maintained into adulthood
via decreased methylation of the IL-10 gene specifically
within microglia. The effect of neonatal handling is
mimicked by pharmacological modulation of glia in adulthood
with ibudilast, which increases IL-10 expression, inhibits
morphine-induced glial activation within the NAcc, and
prevents reinstatement of morphine CPP. Taken together, we
have identified a novel gene × early-life environment
interaction on morphine-induced glial activation and a
specific role for glial activation in drug-induced
reinstatement of drug-seeking behavior.},
Doi = {10.1523/JNEUROSCI.3297-11.2011},
Key = {fds250832}
}
@article{fds250823,
Author = {Williamson, LL and Sholar, PW and Mistry, RS and Smith, SH and Bilbo,
SD},
Title = {Microglia and memory: modulation by early-life
infection.},
Journal = {J Neurosci},
Volume = {31},
Number = {43},
Pages = {15511-15521},
Year = {2011},
Month = {October},
ISSN = {1529-2401},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22031897},
Abstract = {The proinflammatory cytokine interleukin-1β (IL-1β) is
critical for normal hippocampus (HP)-dependent cognition,
whereas high levels can disrupt memory and are implicated in
neurodegeneration. However, the cellular source of IL-1β
during learning has not been shown, and little is known
about the risk factors leading to cytokine dysregulation
within the HP. We have reported that neonatal bacterial
infection in rats leads to marked HP-dependent memory
deficits in adulthood. However, deficits are only observed
if unmasked by a subsequent immune challenge
[lipopolysaccharide (LPS)] around the time of learning.
These data implicate a long-term change within the immune
system that, upon activation with the "second hit," LPS,
acutely impacts the neural processes underlying memory.
Indeed, inhibiting brain IL-1β before the LPS challenge
prevents memory impairment in neonatally infected (NI) rats.
We aimed to determine the cellular source of IL-1β during
normal learning and thereby lend insight into the mechanism
by which this cytokine is enduringly altered by early-life
infection. We show for the first time that CD11b(+) enriched
cells are the source of IL-1β during normal HP-dependent
learning. CD11b(+) cells from NI rats are functionally
sensitized within the adult HP and produce exaggerated
IL-1β ex vivo compared with controls. However, an
exaggerated IL-1β response in vivo requires LPS before
learning. Moreover, preventing microglial activation during
learning prevents memory impairment in NI rats, even
following an LPS challenge. Thus, early-life events can
significantly modulate normal learning-dependent cytokine
activity within the HP, via a specific, enduring impact on
brain microglial function.},
Language = {eng},
Doi = {10.1523/JNEUROSCI.3688-11.2011},
Key = {fds250823}
}
@article{fds250842,
Author = {Bilbo, SD and Wray, GA and Perkins, SE and Parker,
W},
Title = {Reconstitution of the human biome as the most reasonable
solution for epidemics of allergic and autoimmune
diseases.},
Journal = {Med Hypotheses},
Volume = {77},
Number = {4},
Pages = {494-504},
Year = {2011},
Month = {October},
ISSN = {1532-2777},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21741180},
Abstract = {A wide range of hyperimmune-associated diseases plague
post-industrial society, with a prevalence and impact that
is staggering. Strong evidence points towards a loss of
helminths from the ecosystem of the human body (the human
biome) as the most important factor in this epidemic.
Helminths, intestinal worms which are largely eradicated by
elements of post-industrial culture including toilets and
water treatment facilities, have an otherwise ubiquitous
presence in vertebrates, and have co-evolved with the immune
system. Not only do helminths discourage allergic and
autoimmune reactions by diverting the immune system away
from these pathologic processes and stimulating host
regulatory networks, helminths release a variety of factors
which down-modulate the immune system. A comprehensive view
of hyperimmune-related disease based on studies in
immunology, parasitology, evolutionary biology,
epidemiology, and neurobiology indicates that the effects of
biome depletion may not yet be fully realized, and may have
an unexpectedly broad impact on many areas of human biology,
including cognition. Fortunately, colonization with
helminths results in a cure of numerous autoimmune and
allergic diseases in laboratory rodents, and clinical
studies in humans have indicated their utility for treatment
of both multiple sclerosis and inflammatory bowel disease.
Based on these considerations, commitment of considerable
resources toward understanding the effects of "biome
depletion" and systematically evaluating the most effective
approach toward biome reconstitution is strongly
encouraged.},
Language = {eng},
Doi = {10.1016/j.mehy.2011.06.019},
Key = {fds250842}
}
@article{fds250843,
Author = {Bilbo, SD and Smith, SH and Schwarz, JM},
Title = {A Lifespan Approach to Neuroinflammatory and Cognitive
Disorders: A Critical Role for Glia.},
Journal = {Journal of neuroimmune pharmacology : the official journal
of the Society on NeuroImmune Pharmacology},
Volume = {31},
Number = {43},
Pages = {15511-15521},
Year = {2011},
Month = {August},
ISSN = {1557-1904},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21822589},
Abstract = {Cognitive decline is a common problem of aging. Whereas
multiple neural and glial mechanisms may account for these
declines, microglial sensitization and/or dystrophy has
emerged as a leading culprit in brain aging and dysfunction.
However, glial activation is consistently observed in normal
brain aging as well, independent of frank neuroinflammation
or functional impairment. Such variability suggests the
existence of additional vulnerability factors that can
impact neuronal-glial interactions and thus overall brain
and cognitive health. The goal of this review is to
elucidate our working hypothesis that an individual's risk
or resilience to neuroinflammatory disorders and poor
cognitive aging may critically depend on their early life
experience, which can change immune reactivity within the
brain for the remainder of the lifespan. For instance,
early-life infection in rats can profoundly disrupt memory
function in young adulthood, as well as accelerate
age-related cognitive decline, both of which are linked to
enduring changes in glial function that occur in response to
the initial infection. We discuss these findings within the
context of the growing literature on the role of immune
molecules and neuroimmune crosstalk in normal brain
development. We highlight the intrinsic factors (e.g.,
chemokines, hormones) that regulate microglial development
and their colonization of the embryonic and postnatal brain,
and the capacity for disruption or "re-programming" of this
crucial process by external events (e.g., stress,
infection). An impact on glia, which in turn alters neural
development, has the capacity to profoundly impact cognitive
and mental health function at all stages of
life.},
Language = {ENG},
Doi = {10.1007/s11481-011-9299-y},
Key = {fds250843}
}
@article{fds250841,
Author = {Schwarz, JM and Bilbo, SD},
Title = {LPS elicits a much larger and broader inflammatory response
than Escherichia coli infection within the hippocampus of
neonatal rats.},
Journal = {Neuroscience letters},
Volume = {497},
Number = {2},
Pages = {110-115},
Year = {2011},
Month = {June},
ISSN = {1872-7972},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21536105},
Abstract = {An immune challenge during the neonatal period can
significantly affect the development of the nervous and
immune systems, such that long-term abnormalities in immune
function and behavior persist into adulthood. Given that
immune activation and individual cytokines have been linked
to the etiology of many developmental neuropsychiatric
disorders, a complete characterization of the neonatal
immune response within the brain is warranted. In this
study, rats were treated peripherally on postnatal day (P) 4
with either a live Escherichia coli (E. coli) infection or
lipopolysaccharide (LPS), two common models of neonatal
immune activation. Inflammatory gene expression was measured
within the hippocampus 2 and 24h later. We determined that
E. coli and LPS produce very distinct inflammatory profiles
within the brain. Infection with E. coli produced a robust,
yet relatively IL-1 pathway focused activation of the
neonatal immune system within the brain, while LPS produced
a very broad and robust immune response within the brain.
This analysis also identified common inflammatory genes
up-regulated by both E. coli and LPS treatment.},
Language = {eng},
Doi = {10.1016/j.neulet.2011.04.042},
Key = {fds250841}
}
@article{fds250817,
Author = {Bilbo, SD},
Title = {How cytokines leave their mark: the role of the placenta in
developmental programming of brain and behavior.},
Journal = {Brain, behavior, and immunity},
Volume = {25},
Number = {4},
Pages = {602-603},
Year = {2011},
Month = {May},
ISSN = {1090-2139},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21296146},
Keywords = {Animals • Communicable Diseases • Cytokines •
Decidua • Female • Fetal Development • Humans
• Infection • Maternal Exposure • Placenta
• Pregnancy • Prenatal Exposure Delayed Effects
• immunology • immunology*},
Abstract = {An immune challenge during the neonatal period can
significantly affect the development of the nervous and
immune systems, such that long-term abnormalities in immune
function and behavior persist into adulthood. Given that
immune activation and individual cytokines have been linked
to the etiology of many developmental neuropsychiatric
disorders, a complete characterization of the neonatal
immune response within the brain is warranted. In this
study, rats were treated peripherally on postnatal day (P) 4
with either a live Escherichia coli (E. coli) infection or
lipopolysaccharide (LPS), two common models of neonatal
immune activation. Inflammatory gene expression was measured
within the hippocampus 2 and 24h later. We determined that
E. coli and LPS produce very distinct inflammatory profiles
within the brain. Infection with E. coli produced a robust,
yet relatively IL-1 pathway focused activation of the
neonatal immune system within the brain, while LPS produced
a very broad and robust immune response within the brain.
This analysis also identified common inflammatory genes
up-regulated by both E. coli and LPS treatment.},
Language = {eng},
Doi = {10.1016/j.bbi.2011.01.018},
Key = {fds250817}
}
@article{fds250840,
Author = {Bilbo, SD},
Title = {Early-life infection is a vulnerability factor for
aging-related glial alterations and cognitive
decline.},
Journal = {Neurobiology of learning and memory},
Volume = {94},
Number = {1},
Pages = {57-64},
Year = {2010},
Month = {July},
ISSN = {1095-9564},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20388544},
Keywords = {Aging* • Animals • Animals, Newborn • Anxiety
• Brain • Cognition Disorders • Conditioning,
Classical • Escherichia coli Infections • Fear
• Infection* • Male • Maze Learning •
Memory • Memory Disorders • Neuroglia •
Neuropsychological Tests • Rats • Receptors,
N-Methyl-D-Aspartate • Time Factors • metabolism
• metabolism* • physiology • physiopathology
• physiopathology*},
Abstract = {There is significant individual variability in cognitive
decline during aging, suggesting the existence of
"vulnerability factors" for eventual deficits.
Neuroinflammation may be one such factor; increased glial
reactivity is a common outcome of aging, which in turn is
associated with numerous neurodegenerative conditions.
Early-life infection leads to cognitive impairment in
conjunction with an inflammatory challenge in young
adulthood, which led us to explore whether it might also
accelerate the cognitive decline associated with aging. Rats
were treated on postnatal day 4 with PBS or Escherichia
coli, and then tested for learning and memory at 2 or
16months of age, using two fear-conditioning tasks (context
pre-exposure and ambiguous cue), and a spatial water maze
task. Neonatally-infected rats exhibited memory impairments
in both the ambiguous cue fear-conditioning task and in the
water maze, but only at 16months. There were no differences
in anxiety between groups. Neonatally-infected rats also
exhibited greater aging-induced increases in glial markers
(CD11b and MHCII on microglia, and GFAP on astrocytes), as
well as selective changes in NMDA receptor subunit
expression within the hippocampus, but not in amygdala or
parietal cortex compared to controls. Taken together, these
data suggest that early-life infection leads to less
successful cognitive aging, which may be linked to changes
in glial reactivity.},
Language = {eng},
Doi = {10.1016/j.nlm.2010.04.001},
Key = {fds250840}
}
@article{fds250822,
Author = {Bilbo, SD and Tsang, V},
Title = {Enduring consequences of maternal obesity for brain
inflammation and behavior of offspring.},
Journal = {FASEB J},
Volume = {24},
Number = {6},
Pages = {2104-2115},
Year = {2010},
Month = {June},
ISSN = {1530-6860},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20124437},
Keywords = {Animals • Animals, Newborn • Behavior, Animal*
• Brain • Cytokines • Diet, Fat-Restricted
• Dietary Fats • Energy Metabolism • Female
• Leptin • Male • Maternal Nutritional
Physiological Phenomena* • Obesity • Phenotype
• Pregnancy • Prenatal Exposure Delayed Effects
• Rats • Rats, Sprague-Dawley • Weaning
• administration & dosage* • immunology* •
metabolism • pathology* • physiopathology*},
Abstract = {Obesity is well characterized as a systemic inflammatory
condition, and is also associated with cognitive disruption,
suggesting a link between the two. We assessed whether
peripheral inflammation in maternal obesity may be
transferred to the offspring brain, in particular, the
hippocampus, and thereby result in cognitive dysfunction.
Rat dams were fed a high-saturated-fat diet (SFD), a
high-trans-fat diet (TFD), or a low-fat diet (LFD) for 4 wk
prior to mating, and remained on the diet throughout
pregnancy and lactation. SFD/TFD exposure significantly
increased body weight in both dams and pups compared to
controls. Microglial activation markers were increased in
the hippocampus of SFD/TFD pups at birth. At weaning and in
adulthood, proinflammatory cytokine expression was
strikingly increased in the periphery and hippocampus
following a bacterial challenge [lipopolysaccharide (LPS)]
in the SFD/TFD groups compared to controls. Microglial
activation within the hippocampus was also increased basally
in SFD rats, suggesting a chronic priming of the cells.
Finally, there were marked changes in anxiety and spatial
learning in SFD/TFD groups. These effects were all observed
in adulthood, even after the pups were placed on standard
chow at weaning, suggesting these outcomes were programmed
early in life.},
Language = {eng},
Doi = {10.1096/fj.09-144014},
Key = {fds250822}
}
@article{fds250836,
Author = {Bilbo, SD and Wieseler, JL and Barrientos, RM and Tsang, V and Watkins,
LR and Maier, SF},
Title = {Neonatal bacterial infection alters fever to live and
simulated infections in adulthood.},
Journal = {Psychoneuroendocrinology},
Volume = {35},
Number = {3},
Pages = {369-381},
Year = {2010},
Month = {April},
ISSN = {1873-3360},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19682802},
Keywords = {Age Factors • Animals • Animals, Newborn •
Bacterial Infections • Cyclooxygenase 2 •
Escherichia coli • Escherichia coli Infections •
Female • Fever* • Immune Tolerance •
Immunologic Memory • Inflammation •
Lipopolysaccharides • Male • Neuroimmunomodulation
• Rats • Rats, Sprague-Dawley • Weight Loss
• chemically induced • complications • drug
effects • etiology • genetics • immunology
• immunology* • metabolism • pharmacology*
• physiology • physiology* •
physiopathology},
Abstract = {Fever is a critical component of the host immune response to
infection. An emerging literature demonstrates that
experience with infectious organisms early in life, during
the perinatal period, may permanently program immune
responses later in life, including fever. We explored the
influence of neonatal infection with Escherichia coli on
fever responses to lipopolysaccharide (LPS) and E. coli in
adulthood. Fever to a low dose of LPS in adulthood did not
significantly differ as a consequence of early-life
infection. Eight days after the LPS injection, the same
group of rats received a high dose of live E. coli. This
time, neonatally infected rats exhibited a markedly longer
fever than controls. In a subsequent experiment, fever to a
single high dose of E. coli without prior LPS in adulthood
did not differ by group, suggesting that the previous
difference was a lack of tolerance to the dual challenges in
early-infected rats. Finally, both groups exhibited
decreased tumor necrosis factor (TNF)-alpha and
toll-like-receptor (TLR) 4 production to dual LPS challenges
in isolated splenocytes, whereas only rats infected as
neonates exhibited increased cyclooxygenase-2 within the
hypothalamus in response to adult infection, suggesting that
early infection-induced changes in fever regulation may
involve a change in central mechanisms. Taken together,
these data indicate that early-life infection is associated
with marked changes in host temperature regulation in
adulthood.},
Language = {eng},
Doi = {10.1016/j.psyneuen.2009.07.014},
Key = {fds250836}
}
@article{fds250839,
Author = {Bland, ST and Beckley, JT and Watkins, LR and Maier, SF and Bilbo,
SD},
Title = {Neonatal Escherichia coli infection alters glial, cytokine,
and neuronal gene expression in response to acute
amphetamine in adolescent rats.},
Journal = {Neuroscience letters},
Volume = {474},
Number = {1},
Pages = {52-57},
Year = {2010},
Month = {April},
ISSN = {1872-7972},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20223277},
Keywords = {Age Factors • Amphetamine • Animals •
Animals, Newborn • Antigens, CD • Antigens, CD11b
• Central Nervous System Stimulants • Cytokines
• Cytoskeletal Proteins • Escherichia coli
Infections • Gene Expression • Glial Fibrillary
Acidic Protein • Male • Membrane Proteins •
Nerve Tissue Proteins • Neuroglia • Neurons •
RNA, Messenger • Rats • biosynthesis •
biosynthesis* • complications • drug effects*
• genetics • immunology* • metabolism •
metabolism* • pharmacology*},
Abstract = {Neonatal bacterial infection in rats alters the responses to
a variety of subsequent challenges later in life. Here we
explored the effects of neonatal bacterial infection on a
subsequent drug challenge during adolescence, using
administration of the psychostimulant amphetamine. Male rat
pups were injected on postnatal day 4 (P4) with live
Escherichia coli (E. coli) or PBS vehicle, and then received
amphetamine (15mg/kg) or saline on P40. Quantitative RT-PCR
was performed on micropunches taken from medial prefrontal
cortex, nucleus accumbens, and the CA1 subfield of the
hippocampus. mRNA for glial and neuronal activation markers
as well as pro-inflammatory and anti-inflammatory cytokines
were assessed. Amphetamine produced brain region specific
increases in many of these genes in PBS controls, while
these effects were blunted or absent in neonatal E. coli
treated rats. In contrast to the potentiating effect of
neonatal E. coli on glial and cytokine responses to an
immune challenge previously observed, neonatal E. coli
infection attenuates glial and cytokine responses to an
amphetamine challenge.},
Language = {eng},
Doi = {10.1016/j.neulet.2010.03.006},
Key = {fds250839}
}
@article{fds250838,
Author = {Bland, ST and Beckley, JT and Young, S and Tsang, V and Watkins, LR and Maier, SF and Bilbo, SD},
Title = {Enduring consequences of early-life infection on glial and
neural cell genesis within cognitive regions of the
brain.},
Journal = {Brain, behavior, and immunity},
Volume = {24},
Number = {3},
Pages = {329-338},
Year = {2010},
Month = {March},
ISSN = {1090-2139},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19782746},
Keywords = {Animals • Animals, Newborn • Antimetabolites
• Brain • Bromodeoxyuridine • Cell Count
• Cell Proliferation • Cell Survival •
Central Nervous System Infections • Cognition •
Escherichia coli Infections • Female •
Immunohistochemistry • Lipopolysaccharides • Male
• Neuroglia • Neurons • Phenotype • Rats
• Rats, Sprague-Dawley • diagnostic use •
pathology* • pharmacology • physiology •
physiology* • psychology*},
Abstract = {Systemic infection with Escherichia coli on postnatal day
(P) 4 in rats results in significantly altered brain
cytokine responses and behavioral changes in adulthood, but
only in response to a subsequent immune challenge with
lipopolysaccharide [LPS]. The basis for these changes may be
long-term changes in glial cell function. We assessed glial
and neural cell genesis in the hippocampus, parietal cortex
(PAR), and prefrontal cortex (PFC), in neonates just after
the infection, as well as in adulthood in response to LPS.
E. coli increased the number of newborn microglia within the
hippocampus and PAR compared to controls. The total number
of microglia was also significantly increased in E.
coli-treated pups, with a concomitant decrease in total
proliferation. On P33, there were large decreases in numbers
of cells coexpressing BrdU and NeuN in all brain regions of
E. coli rats compared to controls. In adulthood, basal
neurogenesis within the dentate gyrus (DG) did not differ
between groups; however, in response to LPS, there was a
decrease in neurogenesis in early-infected rats, but an
increase in controls to the same challenge. There were also
significantly more microglia in the adult DG of
early-infected rats, although microglial proliferation in
response to LPS was increased in controls. Taken together,
we have provided evidence that systemic infection with E.
coli early in life has significant, enduring consequences
for brain development and subsequent adult function. These
changes include marked alterations in glia, as well as
influences on neurogenesis in brain regions important for
cognition.},
Language = {eng},
Doi = {10.1016/j.bbi.2009.09.012},
Key = {fds250838}
}
@article{fds250798,
Author = {Bilbo, SD},
Title = {Early life environment influences on neuroimmune
interactions and behavior in adulthood},
Journal = {INTEGRATIVE AND COMPARATIVE BIOLOGY},
Volume = {49},
Pages = {E15-E15},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2009},
Month = {February},
ISSN = {1540-7063},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000268808800061&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds250798}
}
@article{fds250837,
Author = {Bilbo, SD and Schwarz, JM},
Title = {Early-life programming of later-life brain and behavior: a
critical role for the immune system.},
Journal = {Frontiers in behavioral neuroscience},
Volume = {3},
Number = {3},
Pages = {14},
Year = {2009},
Month = {January},
ISSN = {1662-5153},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19738918},
Keywords = {Animals • Animals, Newborn • Antimetabolites
• Brain • Bromodeoxyuridine • Cell Count
• Cell Proliferation • Cell Survival •
Central Nervous System Infections • Cognition •
Escherichia coli Infections • Female •
Immunohistochemistry • Lipopolysaccharides • Male
• Neuroglia • Neurons • Phenotype • Rats
• Rats, Sprague-Dawley • diagnostic use •
pathology* • pharmacology • physiology •
physiology* • psychology*},
Abstract = {The immune system is well characterized for its critical
role in host defense. Far beyond this limited role however,
there is mounting evidence for the vital role the immune
system plays within the brain, in both normal, "homeostatic"
processes (e.g., sleep, metabolism, memory), as well as in
pathology, when the dysregulation of immune molecules may
occur. This recognition is especially critical in the area
of brain development. Microglia and astrocytes, the primary
immunocompetent cells of the CNS, are involved in every
major aspect of brain development and function, including
synaptogenesis, apoptosis, and angiogenesis. Cytokines such
as tumor necrosis factor (TNF)alpha, interleukin [IL]-1beta,
and IL-6 are produced by glia within the CNS, and are
implicated in synaptic formation and scaling, long-term
potentiation, and neurogenesis. Importantly, cytokines are
involved in both injury and repair, and the conditions
underlying these distinct outcomes are under intense
investigation and debate. Evidence from both animal and
human studies implicates the immune system in a number of
disorders with known or suspected developmental origins,
including schizophrenia, anxiety/depression, and cognitive
dysfunction. We review the evidence that infection during
the perinatal period of life acts as a vulnerability factor
for later-life alterations in cytokine production, and
marked changes in cognitive and affective behaviors
throughout the remainder of the lifespan. We also discuss
the hypothesis that long-term changes in brain glial cell
function underlie this vulnerability.},
Language = {eng},
Doi = {10.3389/neuro.08.014.2009},
Key = {fds250837}
}
@article{fds250835,
Author = {Bilbo, SD and Barrientos, RM and Eads, AS and Northcutt, A and Watkins,
LR and Rudy, JW and Maier, SF},
Title = {Early-life infection leads to altered BDNF and IL-1beta mRNA
expression in rat hippocampus following learning in
adulthood.},
Journal = {Brain, behavior, and immunity},
Volume = {22},
Number = {4},
Pages = {451-455},
Year = {2008},
Month = {May},
ISSN = {1090-2139},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17997277},
Keywords = {Age Factors • Animals • Animals, Newborn •
Brain-Derived Neurotrophic Factor • Conditioning
(Psychology) • Endotoxemia • Escherichia coli
Infections • Fear • Female • Gene Expression
Regulation • Hippocampus • Interleukin-1beta
• Lipopolysaccharides • Male • Memory
Disorders • RNA, Messenger • Rats • Rats,
Sprague-Dawley • genetics* • immunology •
immunology* • pharmacology • physiology •
physiology* • physiopathology •
physiopathology*},
Abstract = {Neonatal bacterial infection in rats leads to profound
hippocampal-dependent memory impairments following a
peripheral immune challenge in adulthood. Here, we
determined whether neonatal infection plus an immune
challenge in adult rats is associated with impaired
induction of brain-derived neurotrophic factor (BDNF) within
the hippocampus (CA1, CA3, and dentate gyrus) following fear
conditioning. BDNF is well characterized for its critical
role in learning and memory. Rats injected on postnatal day
4 with PBS (vehicle) or Escherichia coli received as adults
either no conditioning or a single 2min trial of fear
conditioning. Half of the rats in the conditioned group then
received a peripheral injection of 25mug/kg
lipopolysaccharide (LPS) and all were sacrificed 1 or 4h
later. Basal (unconditioned) BDNF mRNA did not differ
between groups. However, following conditioning, neonatal
infection with E. coli led to decreased BDNF mRNA induction
in all regions compared to PBS-treated rats. This decrease
in E. coli-treated rats was accompanied by a large increase
in IL-1beta mRNA in CA1. Taken together, these data indicate
that early infection strongly influences the induction of
IL-1beta and BDNF within distinct regions of the
hippocampus, which likely contribute to observed memory
impairments in adulthood.},
Language = {eng},
Doi = {10.1016/j.bbi.2007.10.003},
Key = {fds250835}
}
@article{fds250844,
Author = {Bilbo, SD and Yirmiya, R and Amat, J and Paul, ED and Watkins, LR and Maier, SF},
Title = {Bacterial infection early in life protects against
stressor-induced depressive-like symptoms in adult
rats.},
Journal = {Psychoneuroendocrinology},
Volume = {33},
Number = {3},
Pages = {261-269},
Year = {2008},
Month = {April},
ISSN = {0306-4530},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18164556},
Abstract = {Both early-life stress and immune system activation in
adulthood have been linked independently to depression in a
number of studies. However, the relationship between
early-life infection, which may be considered a "stressor",
and later-life depression has not been explored. We have
reported that neonatal bacterial infection in rats leads to
exaggerated brain cytokine production, as well as memory
impairments, to a subsequent peripheral immune challenge in
adulthood, and therefore predicted that stressor-induced
depressive-like symptoms would be more severe in these rats
as well. Rats treated on postnatal day 4 with PBS or
Escherichia coli were as adults exposed to inescapable
tailshock stress (IS), and then tested for sucrose
preference, social exploration with a juvenile, and overall
activity, 1, 3, 5, and 7 days following the stressor. Serum
corticosterone and extracellular 5-HT within the basolateral
amygdala were measured in a second group of rats in response
to the IS. IS resulted in profound depressive-like behaviors
in adult rats, but, surprisingly, rats that suffered a
bacterial infection early in life had blunted corticosterone
responses to the stressor and were remarkably protected from
the depressive symptoms compared to controls. These data
suggest that early-life infection should be considered
within a cost/benefit perspective, in which outcomes in
adulthood may be differentially protected or impaired. These
data also suggest that the immune system likely plays a
previously unsuspected role in "homeostatic" HPA programming
and brain development, which may ultimately lend insight
into the often-contradictory literature on cytokines,
inflammation, and depression.},
Doi = {10.1016/j.psyneuen.2007.11.008},
Key = {fds250844}
}
@article{fds250834,
Author = {Zala, SM and Chan, BK and Bilbo, SD and Potts, WK and Nelson, RJ and Penn,
DJ},
Title = {Genetic resistance to infection influences a male's sexual
attractiveness and modulation of testosterone.},
Journal = {Brain, behavior, and immunity},
Volume = {22},
Number = {3},
Pages = {381-387},
Year = {2008},
Month = {March},
ISSN = {1090-2139},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17945466},
Keywords = {Animals • Choice Behavior • Female •
Immunity, Innate • Male • Mice • Mice, Inbred
BALB C • Odors • Salmonella Infections •
Scent Glands • Sexual Behavior, Animal* •
Testosterone • Urine • blood • blood* •
genetics* • immunology* • secretion},
Abstract = {Females may be attracted to males genetically resistant to
infectious diseases, and one potential mechanism for this
mating bias is that such males may be better able to
maintain high testosterone. To test these two hypotheses, we
collected scent-marks from male house mice (Mus domesticus)
genetically resistant and susceptible to Salmonella due to a
single locus (Nramp 1, also known as Slc11a1). We tested
whether females are more attracted to the scent-marks of
resistant males, and whether such males are better able to
maintain testosterone concentrations during an experimental
Salmonella infection. We found that females preferred the
scent-marks of genetically resistant males compared to
susceptible ones; but they showed no preferences 5d after
males were infected. As predicted, genetically resistant
males maintained their testosterone concentrations during
the experimental infection, whereas susceptible males showed
a significant decline 14 d after inoculation. These
differences in the males' ability to modulate testosterone,
however, do not explain females' attraction to resistant
males. Thus, our results indicate that females sometimes
prefer males genetically resistant to infection, and they
provide the first evidence that males modulate their
testosterone depending upon their genetic resistance to
infection; however, we found no evidence to link these two
findings.},
Language = {eng},
Doi = {10.1016/j.bbi.2007.09.003},
Key = {fds250834}
}
@article{fds250833,
Author = {Bowers, SL and Bilbo, SD and Dhabhar, FS and Nelson,
RJ},
Title = {Stressor-specific alterations in corticosterone and immune
responses in mice.},
Journal = {Brain, behavior, and immunity},
Volume = {22},
Number = {1},
Pages = {105-113},
Year = {2008},
Month = {January},
ISSN = {1090-2139},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17890050},
Keywords = {Animals • Chronic Disease • Cold Temperature
• Corticosterone • Handling (Psychology) •
Hypersensitivity, Delayed • Leukocyte Count • Male
• Mice • Mice, Inbred C57BL • Monocytes
• Osmolar Concentration • Restraint, Physical
• Skin • Social Isolation • Stress,
Physiological • Swimming • Volition • blood
• blood* • etiology* • immunology* •
pathology},
Abstract = {Different stressors likely elicit different physiological
and behavioral responses. Previously reported differences in
the effects of stressors on immune function may reflect
qualitatively different physiological responses to
stressors; alternatively, both large and subtle differences
in testing protocols and methods among laboratories may make
direct comparisons among studies difficult. Here we examine
the effects of chronic stressors on plasma corticosterone
concentrations, leukocyte redistribution, and skin
delayed-type hypersensitivity (DTH), and the effects of
acute stressors on plasma corticosterone and leukocyte
redistribution. The effects of several commonly used
laboratory stressors including restraint, forced swim,
isolation, and low ambient temperatures (4 degrees C) were
examined. Exposure to each stressor elevated corticosterone
concentrations, with restraint (a putative psychological
stressor) evoking a significantly higher glucocorticoid
response than other stressors. Chronic restraint and forced
swim enhanced the DTH response compared to the handled, low
temperature, or isolation conditions. Restraint, low
temperature, and isolation significantly increased
trafficking of lymphocytes and monocytes compared to forced
swim or handling. Generally, acute restraint, low
temperature, isolation, and handling increased trafficking
of lymphocytes and monocytes. Considered together, our
results suggest that the different stressors commonly used
in psychoneuroimmunology research may not activate the
physiological stress response to the same extent. The
variation observed in the measured immune responses may
reflect differential glucocorticoid activation, differential
metabolic adjustments, or both processes in response to
specific stressors.},
Language = {eng},
Doi = {10.1016/j.bbi.2007.07.012},
Key = {fds250833}
}
@article{fds197406,
Author = {SD Bilbo and NJ Newsum and DB Sprunger and LR Watkins and JW Rudy and SF
Maier},
Title = {Differential effects of neonatal handling on early life
infection-induced alterations in cognition in
adulthood.},
Journal = {Brain, behavior, and immunity},
Volume = {21},
Number = {3},
Pages = {332-42},
Year = {2007},
Month = {March},
ISSN = {0889-1591},
url = {http://dx.doi.org/10.1016/j.bbi.2006.10.005},
Keywords = {Age Factors • Analysis of Variance • Animals
• Animals, Newborn • Bacterial Infections •
Behavior, Animal • Cognition • Critical Period
(Psychology) • Fear • Female • Handling
(Psychology) • Hippocampus • Interleukin-10 •
Learning • Lipopolysaccharides • Male •
Neuroglia • Neuroimmunomodulation • Rats •
Rats, Sprague-Dawley • Stress, Psychological •
immunology • immunology* • metabolism •
physiology • physiology*},
Abstract = {We have previously demonstrated that bacterial infection
(Escherichia coli) in neonatal rats is associated with
impaired memory in a fear-conditioning task in adulthood.
This impairment, however, is only observed if a peripheral
immune challenge (lipopolysaccharide; LPS) is administered
around the time of learning. We used a brief
separation/handling paradigm to determine if the adult
memory impairment associated with neonatal-infection could
be prevented. Naturally occurring variations in maternal
care promote striking variations in offspring cognitive
development, and handling paradigms are used to manipulate
the quality and quantity of maternal care. Rats were
injected on post natal (P) day 4 with E. coli or PBS, and
half from each group were handled for 15 min/day from P4 to
20. All rats were then tested in adulthood. Neonatal
handling of rats infected as neonates prevented the increase
in microglial cell marker reactivity within the hippocampus,
and the exaggerated brain IL-1beta production to LPS
normally produced by the infection. Thus, these neural
processes were now comparable to levels of non-infected PBS
controls. Furthermore, handling completely prevented
LPS-induced memory impairment in a context-fear task in
adult rats infected as neonates. Finally, neonatal handling
dramatically improved spatial learning and memory and
decreased anxiety in rats treated early with PBS, but had no
beneficial effect on these measures in rats infected as
neonates. Taken together, these data suggest that maternal
care may profoundly influence neuroinflammatory processes in
adulthood, and that infection may also prevent maternal care
influences on cognition later in life.},
Language = {eng},
Doi = {10.1016/j.bbi.2006.10.005},
Key = {fds197406}
}
@article{fds250846,
Author = {Bilbo, SD and Newsum, NJ and Sprunger, DB and Watkins, LR and Rudy, JW and Maier, SF},
Title = {Differential effects of neonatal handling on early life
infection-induced alterations in cognition in
adulthood.},
Journal = {Brain, behavior, and immunity},
Volume = {21},
Number = {3},
Pages = {332-342},
Year = {2007},
Month = {March},
ISSN = {0889-1591},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17126527},
Abstract = {We have previously demonstrated that bacterial infection
(Escherichia coli) in neonatal rats is associated with
impaired memory in a fear-conditioning task in adulthood.
This impairment, however, is only observed if a peripheral
immune challenge (lipopolysaccharide; LPS) is administered
around the time of learning. We used a brief
separation/handling paradigm to determine if the adult
memory impairment associated with neonatal-infection could
be prevented. Naturally occurring variations in maternal
care promote striking variations in offspring cognitive
development, and handling paradigms are used to manipulate
the quality and quantity of maternal care. Rats were
injected on post natal (P) day 4 with E. coli or PBS, and
half from each group were handled for 15 min/day from P4 to
20. All rats were then tested in adulthood. Neonatal
handling of rats infected as neonates prevented the increase
in microglial cell marker reactivity within the hippocampus,
and the exaggerated brain IL-1beta production to LPS
normally produced by the infection. Thus, these neural
processes were now comparable to levels of non-infected PBS
controls. Furthermore, handling completely prevented
LPS-induced memory impairment in a context-fear task in
adult rats infected as neonates. Finally, neonatal handling
dramatically improved spatial learning and memory and
decreased anxiety in rats treated early with PBS, but had no
beneficial effect on these measures in rats infected as
neonates. Taken together, these data suggest that maternal
care may profoundly influence neuroinflammatory processes in
adulthood, and that infection may also prevent maternal care
influences on cognition later in life.},
Doi = {10.1016/j.bbi.2006.10.005},
Key = {fds250846}
}
@article{fds250801,
Author = {Bilbo, SD and Newsum, NJ and Mahoney, JH and Sprunger, DP and Watkins,
LR and Rudy, JW and Maier, SF},
Title = {Maternal care modulation of neonatal infection-facilitated
cognitive impairment in adulthood},
Journal = {Frontiers in Neuroendocrinology},
Volume = {27},
Number = {1},
Pages = {107-107},
Publisher = {Elsevier BV},
Year = {2006},
Month = {May},
ISSN = {0091-3022},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000238456300205&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Doi = {10.1016/j.yfrne.2006.03.265},
Key = {fds250801}
}
@article{fds197407,
Author = {SD Bilbo and JW Rudy and LR Watkins and SF Maier},
Title = {A behavioural characterization of neonatal
infection-facilitated memory impairment in adult
rats.},
Journal = {Behavioural brain research},
Volume = {169},
Number = {1},
Pages = {39-47},
Year = {2006},
Month = {April},
ISSN = {0166-4328},
url = {http://dx.doi.org/10.1016/j.bbr.2005.12.002},
Keywords = {Age Factors • Amnesia, Retrograde • Animals •
Animals, Newborn • Association Learning •
Bacterial Infections • Behavior, Animal •
Conditioning, Classical • Critical Period (Psychology)
• Disease Models, Animal • Fear • Female
• Hippocampus • Lipopolysaccharides • Male
• Rats • Rats, Sprague-Dawley • complications
• etiology • immunology • immunology* •
physiology • physiology* • physiopathology},
Abstract = {We have reported that exposure to bacteria (Escherichia
coli) during the neonatal period in rats is associated with
impaired memory for a novel context in adulthood. However,
impairment is only observed if a peripheral immune challenge
(bacterial lipopolysaccharide (LPS)) is administered
immediately following context exposure. The goal of the
current study was to more fully characterize this
phenomenon. In Experiment 1, memory impairment as a result
of neonatal infection and subsequent LPS challenge was
observed in juvenile rats, indicating that the changes
induced by infection occur early on and are then manifest
throughout the lifespan. In Experiment 2, infection in
juvenile rats did not lead to LPS-induced memory impairment
in adulthood, suggesting there is a critical period for
early infection-induced alterations. In Experiments 3 and 4,
memory for a novel context was impaired in neonatally
infected rats, a task that is dependent on the hippocampus,
whereas cued memory for a tone, which does not depend on the
hippocampus, was not impaired. Furthermore, long-term, but
not short-term contextual memory was impaired in adult rats
infected as neonates following an LPS challenge either 24 h
before or immediately after conditioning. Finally, in
Experiment 5, no neonatal group differences were observed in
corticosterone or open field behaviour, suggesting that
decreased freezing to a conditioned context reflects
impaired memory, and not simply hyperactivity or altered
stress reactivity. Taken together, we have demonstrated that
neonatal infection results in robust hippocampal-dependent
memory impairment following an immune challenge in adulthood
using a number of conditioning paradigms.},
Language = {eng},
Doi = {10.1016/j.bbr.2005.12.002},
Key = {fds197407}
}
@article{fds250845,
Author = {Bilbo, SD and Rudy, JW and Watkins, LR and Maier,
SF},
Title = {A behavioural characterization of neonatal
infection-facilitated memory impairment in adult
rats.},
Journal = {Behavioural brain research},
Volume = {169},
Number = {1},
Pages = {39-47},
Year = {2006},
Month = {April},
ISSN = {0166-4328},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16413067},
Abstract = {We have reported that exposure to bacteria (Escherichia
coli) during the neonatal period in rats is associated with
impaired memory for a novel context in adulthood. However,
impairment is only observed if a peripheral immune challenge
(bacterial lipopolysaccharide (LPS)) is administered
immediately following context exposure. The goal of the
current study was to more fully characterize this
phenomenon. In Experiment 1, memory impairment as a result
of neonatal infection and subsequent LPS challenge was
observed in juvenile rats, indicating that the changes
induced by infection occur early on and are then manifest
throughout the lifespan. In Experiment 2, infection in
juvenile rats did not lead to LPS-induced memory impairment
in adulthood, suggesting there is a critical period for
early infection-induced alterations. In Experiments 3 and 4,
memory for a novel context was impaired in neonatally
infected rats, a task that is dependent on the hippocampus,
whereas cued memory for a tone, which does not depend on the
hippocampus, was not impaired. Furthermore, long-term, but
not short-term contextual memory was impaired in adult rats
infected as neonates following an LPS challenge either 24 h
before or immediately after conditioning. Finally, in
Experiment 5, no neonatal group differences were observed in
corticosterone or open field behaviour, suggesting that
decreased freezing to a conditioned context reflects
impaired memory, and not simply hyperactivity or altered
stress reactivity. Taken together, we have demonstrated that
neonatal infection results in robust hippocampal-dependent
memory impairment following an immune challenge in adulthood
using a number of conditioning paradigms.},
Doi = {10.1016/j.bbr.2005.12.002},
Key = {fds250845}
}
@article{fds250799,
Author = {Maier, SF and Bilbo, SD},
Title = {The impact of infection early in life on the formation of
long-term memories in adulthood},
Journal = {NEUROPSYCHOPHARMACOLOGY},
Volume = {30},
Pages = {S8-S9},
Publisher = {NATURE PUBLISHING GROUP},
Year = {2005},
Month = {December},
ISSN = {0893-133X},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000233442100024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds250799}
}
@article{fds197409,
Author = {GN Neigh and ER Glasper and SD Bilbo and RJ Traystman and A Courtney
DeVries},
Title = {Cardiac arrest/cardiopulmonary resuscitation augments
cell-mediated immune function and transiently suppresses
humoral immune function.},
Journal = {Journal of cerebral blood flow and metabolism : official
journal of the International Society of Cerebral Blood Flow
and Metabolism},
Volume = {25},
Number = {11},
Pages = {1424-32},
Year = {2005},
Month = {November},
ISSN = {0271-678X},
url = {http://dx.doi.org/10.1038/sj.jcbfm.9600137},
Keywords = {Animals • Antibody Formation • Antigens •
Cardiopulmonary Resuscitation* • Corticosterone •
Heart Arrest • Hippocampus • Humans •
Hypersensitivity, Delayed • Hypothalamo-Hypophyseal
System • Hypothermia • Immunity, Cellular •
Ischemia • Male • Mice • Neurons •
Pituitary-Adrenal System • blood • immunology
• immunology* • injuries • metabolism •
methods • prevention & control •
therapy},
Abstract = {Immune system activation has implications for
cerebrovascular health, but little is known about the
function of the immune system after a major cerebrovascular
event, such as cardiac arrest and cardiopulmonary
resuscitation (CA/CPR). Cardiac arrest and cardiopulmonary
resuscitation damages the hippocampus, an important
component of the hypothalamic-pituitary-adrenal (HPA) axis,
and alterations in HPA axis activity can affect immune
function. We tested the hypothesis that CA/CPR
(approximately 8 mins) would cause HPA axis dysregulation
and alter the delayed type hypersensitivity (DTH) response
to antigenic challenge. We also assessed the primary and
secondary antibody response of mice exposed to CA/CPR. Of
the mice exposed to CA/CPR, half had brains protected by
hypothermia to isolate the effects of the CA/CPR procedure
from the effects of CA/CPR-induced neuronal damage. Cardiac
arrest and cardiopulmonary resuscitation-induced neuronal
damage resulted in a persistent elevation of blood
corticosterone concentration and a concomitant augmentation
of the DTH response to antigenic challenge. Furthermore,
immune activation before CA/CPR decreased survival after
global ischemia. These data highlight the potential impact
of neuronal damage on cell-mediated immune function and the
role of humoral immune activation in outcome after global
ischemia.},
Language = {eng},
Doi = {10.1038/sj.jcbfm.9600137},
Key = {fds197409}
}
@article{fds250852,
Author = {Neigh, GN and Glasper, ER and Bilbo, SD and Traystman, RJ and Courtney
DeVries, A},
Title = {Cardiac arrest/cardiopulmonary resuscitation augments
cell-mediated immune function and transiently suppresses
humoral immune function.},
Journal = {Journal of cerebral blood flow and metabolism : official
journal of the International Society of Cerebral Blood Flow
and Metabolism},
Volume = {25},
Number = {11},
Pages = {1424-1432},
Year = {2005},
Month = {November},
ISSN = {0271-678X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15874972},
Abstract = {Immune system activation has implications for
cerebrovascular health, but little is known about the
function of the immune system after a major cerebrovascular
event, such as cardiac arrest and cardiopulmonary
resuscitation (CA/CPR). Cardiac arrest and cardiopulmonary
resuscitation damages the hippocampus, an important
component of the hypothalamic-pituitary-adrenal (HPA) axis,
and alterations in HPA axis activity can affect immune
function. We tested the hypothesis that CA/CPR
(approximately 8 mins) would cause HPA axis dysregulation
and alter the delayed type hypersensitivity (DTH) response
to antigenic challenge. We also assessed the primary and
secondary antibody response of mice exposed to CA/CPR. Of
the mice exposed to CA/CPR, half had brains protected by
hypothermia to isolate the effects of the CA/CPR procedure
from the effects of CA/CPR-induced neuronal damage. Cardiac
arrest and cardiopulmonary resuscitation-induced neuronal
damage resulted in a persistent elevation of blood
corticosterone concentration and a concomitant augmentation
of the DTH response to antigenic challenge. Furthermore,
immune activation before CA/CPR decreased survival after
global ischemia. These data highlight the potential impact
of neuronal damage on cell-mediated immune function and the
role of humoral immune activation in outcome after global
ischemia.},
Doi = {10.1038/sj.jcbfm.9600137},
Key = {fds250852}
}
@article{fds197408,
Author = {SD Bilbo and JC Biedenkapp and A Der-Avakian and LR Watkins and JW Rudy and SF Maier},
Title = {Neonatal infection-induced memory impairment after
lipopolysaccharide in adulthood is prevented via caspase-1
inhibition.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {25},
Number = {35},
Pages = {8000-9},
Year = {2005},
Month = {August},
ISSN = {1529-2401},
url = {http://dx.doi.org/10.1523/JNEUROSCI.1748-05.2005},
Keywords = {Age Factors • Animals • Animals, Newborn •
Caspase 1 • Enzyme Inhibitors • Escherichia coli
Infections • Female • Hippocampus •
Interleukin-1 • Lipopolysaccharides • Male •
Memory Disorders • Pregnancy • Rats • Rats,
Sprague-Dawley • antagonists & inhibitors •
antagonists & inhibitors* • chemically induced •
drug effects • drug therapy • enzymology •
enzymology* • metabolism • microbiology •
pharmacology • physiology • prevention & control*
• therapeutic use* • toxicity*},
Abstract = {We have reported that neonatal infection leads to memory
impairment after an immune challenge in adulthood. Here we
explored whether events occurring as a result of early
infection alter the response to a subsequent immune
challenge in adult rats, which may then impair memory. In
experiment 1, peripheral infection with Escherichia coli on
postnatal day 4 increased cytokines and corticosterone in
the periphery, and cytokine and microglial cell marker gene
expression in the hippocampus of neonate pups. Next, rats
treated neonatally with E. coli or PBS were injected in
adulthood with lipopolysaccharide (LPS) or saline and killed
1-24 h later. Microglial cell marker mRNA was elevated in
hippocampus in saline controls infected as neonates.
Furthermore, LPS induced a greater increase in glial cell
marker mRNA in hippocampus of neonatally infected rats, and
this increase remained elevated at 24 h versus controls.
After LPS, neonatally infected rats exhibited faster
increases in interleukin-1beta (IL-1beta) within the
hippocampus and cortex and a prolonged response within the
cortex. There were no group differences in peripheral
cytokines or corticosterone. In experiment 2, rats treated
neonatally with E. coli or PBS received as adults either
saline or a centrally administered caspase-1 inhibitor,
which specifically prevents the synthesis of IL-1beta, 1 h
before a learning event and subsequent LPS challenge.
Caspase-1 inhibition completely prevented LPS-induced memory
impairment in neonatally infected rats. These data implicate
IL-1beta in the set of immune/inflammatory events that occur
in the brain as a result of neonatal infection, which likely
contribute to cognitive alterations in adulthood.},
Language = {eng},
Doi = {10.1523/JNEUROSCI.1748-05.2005},
Key = {fds197408}
}
@article{fds250855,
Author = {Bilbo, SD and Biedenkapp, JC and Der-Avakian, A and Watkins, LR and Rudy, JW and Maier, SF},
Title = {Neonatal infection-induced memory impairment after
lipopolysaccharide in adulthood is prevented via caspase-1
inhibition.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {25},
Number = {35},
Pages = {8000-8009},
Year = {2005},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16135757},
Abstract = {We have reported that neonatal infection leads to memory
impairment after an immune challenge in adulthood. Here we
explored whether events occurring as a result of early
infection alter the response to a subsequent immune
challenge in adult rats, which may then impair memory. In
experiment 1, peripheral infection with Escherichia coli on
postnatal day 4 increased cytokines and corticosterone in
the periphery, and cytokine and microglial cell marker gene
expression in the hippocampus of neonate pups. Next, rats
treated neonatally with E. coli or PBS were injected in
adulthood with lipopolysaccharide (LPS) or saline and killed
1-24 h later. Microglial cell marker mRNA was elevated in
hippocampus in saline controls infected as neonates.
Furthermore, LPS induced a greater increase in glial cell
marker mRNA in hippocampus of neonatally infected rats, and
this increase remained elevated at 24 h versus controls.
After LPS, neonatally infected rats exhibited faster
increases in interleukin-1beta (IL-1beta) within the
hippocampus and cortex and a prolonged response within the
cortex. There were no group differences in peripheral
cytokines or corticosterone. In experiment 2, rats treated
neonatally with E. coli or PBS received as adults either
saline or a centrally administered caspase-1 inhibitor,
which specifically prevents the synthesis of IL-1beta, 1 h
before a learning event and subsequent LPS challenge.
Caspase-1 inhibition completely prevented LPS-induced memory
impairment in neonatally infected rats. These data implicate
IL-1beta in the set of immune/inflammatory events that occur
in the brain as a result of neonatal infection, which likely
contribute to cognitive alterations in adulthood.},
Doi = {10.1523/jneurosci.1748-05.2005},
Key = {fds250855}
}
@article{fds197410,
Author = {SD Bilbo and LH Levkoff and JH Mahoney and LR Watkins and JW Rudy and SF
Maier},
Title = {Neonatal infection induces memory impairments following an
immune challenge in adulthood.},
Journal = {Behavioral neuroscience},
Volume = {119},
Number = {1},
Pages = {293-301},
Year = {2005},
Month = {February},
ISSN = {0735-7044},
url = {http://dx.doi.org/10.1037/0735-7044.119.1.293},
Keywords = {Animals • Astrocytes • Escherichia coli •
Escherichia coli Infections • Female • Hippocampus
• Interleukin-1 • Lipopolysaccharides • Male
• Memory Disorders • Pregnancy • Pregnancy
Complications, Infectious • Prenatal Exposure Delayed
Effects* • Rats • analysis • complications*
• immunology • immunology* • pathogenicity*
• pathology* • pharmacology • physiology
• physiopathology* • poisoning • psychology*
• veterinary},
Abstract = {Exposure to infectious agents during early postnatal life
often alters glucocorticoid responses to stress and immune
outcomes in adulthood. The authors examined whether neonatal
infection results in memory impairments in adult animals.
Rats infected with Escherichia coli (E. coli) as neonates
displayed impaired memory for a recently explored context in
adulthood. This impairment, however, was only observed in
rats that received a peripheral immune challenge
(lipopolysaccharide; LPS) immediately following context
exposure. Adult rats treated neonatally with E. coli also
had decreased hippocampal astrocytes compared with
phosphate-buffered saline-treated rats, but displayed
increased astrocyte reactivity in the hippocampus and
decreased brain interleukin-1beta following
lipopolysaccharide. Infection during development appears to
alter glia within the hippocampus, which may contribute to
altered cytokine responses and memory impairment.},
Language = {eng},
Doi = {10.1037/0735-7044.119.1.293},
Key = {fds197410}
}
@article{fds250854,
Author = {Bilbo, SD and Levkoff, LH and Mahoney, JH and Watkins, LR and Rudy, JW and Maier, SF},
Title = {Neonatal infection induces memory impairments following an
immune challenge in adulthood.},
Journal = {Behavioral neuroscience},
Volume = {119},
Number = {1},
Pages = {293-301},
Year = {2005},
Month = {February},
ISSN = {0735-7044},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15727533},
Abstract = {Exposure to infectious agents during early postnatal life
often alters glucocorticoid responses to stress and immune
outcomes in adulthood. The authors examined whether neonatal
infection results in memory impairments in adult animals.
Rats infected with Escherichia coli (E. coli) as neonates
displayed impaired memory for a recently explored context in
adulthood. This impairment, however, was only observed in
rats that received a peripheral immune challenge
(lipopolysaccharide; LPS) immediately following context
exposure. Adult rats treated neonatally with E. coli also
had decreased hippocampal astrocytes compared with
phosphate-buffered saline-treated rats, but displayed
increased astrocyte reactivity in the hippocampus and
decreased brain interleukin-1beta following
lipopolysaccharide. Infection during development appears to
alter glia within the hippocampus, which may contribute to
altered cytokine responses and memory impairment.},
Doi = {10.1037/0735-7044.119.1.293},
Key = {fds250854}
}
@article{fds197411,
Author = {BJ Prendergast and SD Bilbo and RJ Nelson},
Title = {Short day lengths enhance skin immune responses in
gonadectomised Siberian hamsters.},
Journal = {Journal of neuroendocrinology},
Volume = {17},
Number = {1},
Pages = {18-21},
Year = {2005},
Month = {January},
ISSN = {0953-8194},
url = {http://dx.doi.org/10.1111/j.1365-2826.2005.01273.x},
Keywords = {Androgens • Animals • Cricetinae •
Hypersensitivity, Delayed • Immune System • Male
• Orchiectomy • Periodicity • Phodopus •
Photoperiod* • Skin • Testosterone • drug
effects • immunology* • pharmacology* •
physiology • physiopathology*},
Abstract = {In Siberian hamsters and other photoperiodic rodents,
exposure to short photoperiods simultaneously inhibits
gonadal hormone secretion and enhances some measures of
immune function. The present study tested whether gonadal
hormones mediate the effects of short days on skin immune
function (delayed-type hypersensitivity reactions) in male
Siberian hamsters. The magnitude of delayed-type
hypersensitivity reactions was greater in hamsters exposed
to short days relative to those in long days. Comparable
effects of photoperiod were obtained in castrated hamsters
bearing empty or testosterone-filled implants. The data
suggest that contemporary gonadal hormone secretion is
neither necessary, nor sufficient to mediate the effects of
short photoperiods on skin immune function.},
Language = {eng},
Doi = {10.1111/j.1365-2826.2005.01273.x},
Key = {fds197411}
}
@article{fds250853,
Author = {Prendergast, BJ and Bilbo, SD and Nelson, RJ},
Title = {Short day lengths enhance skin immune responses in
gonadectomised Siberian hamsters.},
Journal = {Journal of neuroendocrinology},
Volume = {17},
Number = {1},
Pages = {18-21},
Year = {2005},
Month = {January},
ISSN = {0953-8194},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15720471},
Abstract = {In Siberian hamsters and other photoperiodic rodents,
exposure to short photoperiods simultaneously inhibits
gonadal hormone secretion and enhances some measures of
immune function. The present study tested whether gonadal
hormones mediate the effects of short days on skin immune
function (delayed-type hypersensitivity reactions) in male
Siberian hamsters. The magnitude of delayed-type
hypersensitivity reactions was greater in hamsters exposed
to short days relative to those in long days. Comparable
effects of photoperiod were obtained in castrated hamsters
bearing empty or testosterone-filled implants. The data
suggest that contemporary gonadal hormone secretion is
neither necessary, nor sufficient to mediate the effects of
short photoperiods on skin immune function.},
Doi = {10.1111/j.1365-2826.2005.01273.x},
Key = {fds250853}
}
@article{fds197412,
Author = {GN Neigh and SD Bilbo and AK Hotchkiss and RJ Nelson},
Title = {Exogenous pyruvate prevents stress-evoked suppression of
mitogen-stimulated proliferation.},
Journal = {Brain, behavior, and immunity},
Volume = {18},
Number = {5},
Pages = {425-33},
Year = {2004},
Month = {September},
ISSN = {0889-1591},
url = {http://dx.doi.org/10.1016/j.bbi.2003.10.001},
Keywords = {Analysis of Variance • Animals • Cell Division
• Corticosterone • Dose-Response Relationship,
Drug • Down-Regulation • Energy Metabolism •
Injections, Intraperitoneal • Lactic Acid • Male
• Mice • Mice, Inbred C57BL • Mitogens •
Pyruvic Acid • Restraint, Physical • Spleen •
Stress, Psychological • administration & dosage* •
blood • cytology* • drug effects • immunology
• metabolism* • pharmacology • physiology
• physiology* • physiopathology •
psychology},
Abstract = {Although the phenomenon that psychological stress influences
disease onset and progression is well established, the
mechanisms underlying stress-evoked compromise of immune
function remain unspecified. To test the hypothesis that
energetic shortages compromise immunity, we evaluated the
effectiveness of pyruvate, a metabolic supplement, to
prevent stress-evoked suppression of mitogen-stimulated
splenocyte proliferation. Male C57BL/6 mice were subjected
to 2h of restraint once daily for 14 days. Consistent with
previous studies, mitogen-stimulated splenocyte
proliferation was reduced after restraint; in contrast, mice
that received pyruvate injections immediately following each
episode of restraint did not reduce splenocyte
proliferation. In addition, restraint-evoked corticosterone
elevation did not habituate in animals treated with
pyruvate, suggesting that glucocorticoids are not
exclusively immunosuppressive. The ratio of pyruvate to
lactate, an index of aerobic metabolism, was elevated in
mice exposed to restraint suggesting that mice exposed to
restraint were preferentially using aerobic metabolism and
producing more ATP per unit of pyruvate than non-restrained
mice. Furthermore, two of the effective doses of pyruvate
(0.5 and 500.0mg/kg) altered glucose levels suggesting a
metabolic function of the supplement. Although several
different mechanisms could possibly mediate the changes in
splenocyte proliferation, these results support the
hypothesis that stress-evoked immunosuppression may be a
function of metabolic energy shortages and can be prevented
via pyruvate supplementation.},
Language = {eng},
Doi = {10.1016/j.bbi.2003.10.001},
Key = {fds197412}
}
@article{fds250847,
Author = {Neigh, GN and Bilbo, SD and Hotchkiss, AK and Nelson,
RJ},
Title = {Exogenous pyruvate prevents stress-evoked suppression of
mitogen-stimulated proliferation.},
Journal = {Brain, behavior, and immunity},
Volume = {18},
Number = {5},
Pages = {425-433},
Year = {2004},
Month = {September},
ISSN = {0889-1591},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15265535},
Abstract = {Although the phenomenon that psychological stress influences
disease onset and progression is well established, the
mechanisms underlying stress-evoked compromise of immune
function remain unspecified. To test the hypothesis that
energetic shortages compromise immunity, we evaluated the
effectiveness of pyruvate, a metabolic supplement, to
prevent stress-evoked suppression of mitogen-stimulated
splenocyte proliferation. Male C57BL/6 mice were subjected
to 2h of restraint once daily for 14 days. Consistent with
previous studies, mitogen-stimulated splenocyte
proliferation was reduced after restraint; in contrast, mice
that received pyruvate injections immediately following each
episode of restraint did not reduce splenocyte
proliferation. In addition, restraint-evoked corticosterone
elevation did not habituate in animals treated with
pyruvate, suggesting that glucocorticoids are not
exclusively immunosuppressive. The ratio of pyruvate to
lactate, an index of aerobic metabolism, was elevated in
mice exposed to restraint suggesting that mice exposed to
restraint were preferentially using aerobic metabolism and
producing more ATP per unit of pyruvate than non-restrained
mice. Furthermore, two of the effective doses of pyruvate
(0.5 and 500.0mg/kg) altered glucose levels suggesting a
metabolic function of the supplement. Although several
different mechanisms could possibly mediate the changes in
splenocyte proliferation, these results support the
hypothesis that stress-evoked immunosuppression may be a
function of metabolic energy shortages and can be prevented
via pyruvate supplementation.},
Doi = {10.1016/j.bbi.2003.10.001},
Key = {fds250847}
}
@article{fds197413,
Author = {BJ Prendergast and SD Bilbo and FS Dhabhar and RJ
Nelson},
Title = {Effects of photoperiod history on immune responses to
intermediate day lengths in Siberian hamsters (Phodopus
sungorus).},
Journal = {Journal of neuroimmunology},
Volume = {149},
Number = {1-2},
Pages = {31-9},
Year = {2004},
Month = {April},
ISSN = {0165-5728},
url = {http://dx.doi.org/10.1016/j.jneuroim.2003.12.006},
Keywords = {Age Factors • Analysis of Variance • Animals
• Animals, Newborn • Behavior, Animal • Body
Weight • Cricetinae • Dinitrobenzenes •
Environment • Enzyme-Linked Immunosorbent Assay •
Female • Hair • Hemocyanin • Immune System
• Immunization • Immunoglobulins • Leukocyte
Count • Leukocytes • Lymphocyte Activation •
Male • Organ Size • Phodopus • Photoperiod*
• Pregnancy • Seasons* • Testis • Time
Factors • blood • immunology • immunology*
• metabolism • methods • pharmacology •
physiology • radiation effects • radiation
effects*},
Abstract = {Seasonal changes in day length enhance or suppress immune
function in individuals of several mammalian species.
Siberian hamsters (Phodopus sungorus) are long-day breeders
that adjust reproductive physiology and behavior, body mass,
and immune function following exposure to short
photoperiods. Photoperiods of intermediate-duration,
encountered in nature by juvenile hamsters born in
early-spring and by those born in mid-summer, trigger
gonadal development in the former cohort and inhibit the
onset of puberty in the latter. Divergent reproductive
responses to the same intermediate photoperiod depend on a
photoperiod history, communicated during gestation. These
experiments assessed whether photoperiod history during
gestation likewise impacts immunological responses to
intermediate photoperiods. Male hamsters were gestated in
long photoperiods and remained in long photoperiods
postnatally, or were transferred to an intermediate-duration
or a short-duration photoperiod; other males were gestated
in short days and transferred to an intermediate-duration
photoperiod at birth. Long days stimulated, and short days
inhibited, somatic and reproductive development;
intermediate day lengths either accelerated or inhibited
somatic and reproductive development, depending on whether
hamsters were gestated in short days or long days,
respectively. By contrast, photoperiod during gestation did
not affect most immune endpoints. The data suggest that
photoperiodic mechanisms that enhance and suppress several
aspects of immunity in young-adult hamsters are not
responsive to prenatally communicated photoperiod history
information.},
Language = {eng},
Doi = {10.1016/j.jneuroim.2003.12.006},
Key = {fds197413}
}
@article{fds250848,
Author = {Prendergast, BJ and Bilbo, SD and Dhabhar, FS and Nelson,
RJ},
Title = {Effects of photoperiod history on immune responses to
intermediate day lengths in Siberian hamsters (Phodopus
sungorus).},
Journal = {Journal of neuroimmunology},
Volume = {149},
Number = {1-2},
Pages = {31-39},
Year = {2004},
Month = {April},
ISSN = {0165-5728},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15020062},
Abstract = {Seasonal changes in day length enhance or suppress immune
function in individuals of several mammalian species.
Siberian hamsters (Phodopus sungorus) are long-day breeders
that adjust reproductive physiology and behavior, body mass,
and immune function following exposure to short
photoperiods. Photoperiods of intermediate-duration,
encountered in nature by juvenile hamsters born in
early-spring and by those born in mid-summer, trigger
gonadal development in the former cohort and inhibit the
onset of puberty in the latter. Divergent reproductive
responses to the same intermediate photoperiod depend on a
photoperiod history, communicated during gestation. These
experiments assessed whether photoperiod history during
gestation likewise impacts immunological responses to
intermediate photoperiods. Male hamsters were gestated in
long photoperiods and remained in long photoperiods
postnatally, or were transferred to an intermediate-duration
or a short-duration photoperiod; other males were gestated
in short days and transferred to an intermediate-duration
photoperiod at birth. Long days stimulated, and short days
inhibited, somatic and reproductive development;
intermediate day lengths either accelerated or inhibited
somatic and reproductive development, depending on whether
hamsters were gestated in short days or long days,
respectively. By contrast, photoperiod during gestation did
not affect most immune endpoints. The data suggest that
photoperiodic mechanisms that enhance and suppress several
aspects of immunity in young-adult hamsters are not
responsive to prenatally communicated photoperiod history
information.},
Doi = {10.1016/j.jneuroim.2003.12.006},
Key = {fds250848}
}
@article{fds197414,
Author = {BJ Prendergast and AK Hotchkiss and SD Bilbo and RJ
Nelson},
Title = {Peripubertal immune challenges attenuate reproductive
development in male Siberian hamsters (Phodopus
sungorus).},
Journal = {Biology of reproduction},
Volume = {70},
Number = {3},
Pages = {813-20},
Year = {2004},
Month = {March},
ISSN = {0006-3363},
url = {http://dx.doi.org/10.1095/biolreprod.103.023408},
Keywords = {Animals • Body Temperature • Body Weight •
Cricetinae • Eating • Female • Hemocyanin
• Immunoglobulin G • Immunoglobulin M • Male
• Phodopus • Photoperiod* • Reproduction
• Sexual Maturation • Testosterone • blood
• immunology • immunology*},
Abstract = {Differential allocation of energy to reproduction versus
host defense is assumed to drive the seasonal antiphase
relation between peak reproductive function and
immunocompetence; however, evidence supporting this
assumption is only correlational. These experiments tested
whether photoperiod affects immune responses to antigens in
peripubertal Siberian hamsters, whether such activation of
the immune system exacts energetic and reproductive costs,
and whether such costs vary seasonally. Male Siberian
hamsters were raised from birth in long (LD) or short days
(SD), which respectively initiate or inhibit the onset of
puberty. To elicit a specific immune response, hamsters were
injected with a novel antigen (keyhole limpet hemocyanin
[KLH]) as juveniles. Reproductive development was attenuated
and body temperature was elevated in LD hamsters relative to
saline-injected control animals. In contrast, KLH treatments
affected neither thermoregulation nor reproductive
development in photoinhibited SD hamsters. In experiment 2,
juvenile male hamsters were challenged with bacterial
lipopolysaccharide (LPS) in order to elicit an innate immune
response. Febrile and anorexic responses to LPS were greater
in reproductively stimulated LD hamsters relative to
reproductively inhibited SD hamsters. LPS treatments
attenuated somatic and testicular development in LD
hamsters, but did not significantly affect circulating
testosterone concentrations. In contrast, LPS treatments
were without effect on somatic and reproductive development
in SD hamsters. These experiments indicate that photoperiod
affects antigen-specific antibody production, febrile
responses to LPS, and sickness behaviors in juvenile
Siberian hamsters, and that peripubertal activation of the
immune system exacts energetic and metabolic costs that can
diminish the magnitude of somatic and reproductive
maturation in LD. The data also underscore the importance of
seasonally dependent life history factors in assessing
physiological tradeoffs.},
Language = {eng},
Doi = {10.1095/biolreprod.103.023408},
Key = {fds197414}
}
@article{fds250849,
Author = {Prendergast, BJ and Hotchkiss, AK and Bilbo, SD and Nelson,
RJ},
Title = {Peripubertal immune challenges attenuate reproductive
development in male Siberian hamsters (Phodopus
sungorus).},
Journal = {Biology of reproduction},
Volume = {70},
Number = {3},
Pages = {813-820},
Year = {2004},
Month = {March},
ISSN = {0006-3363},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14627552},
Abstract = {Differential allocation of energy to reproduction versus
host defense is assumed to drive the seasonal antiphase
relation between peak reproductive function and
immunocompetence; however, evidence supporting this
assumption is only correlational. These experiments tested
whether photoperiod affects immune responses to antigens in
peripubertal Siberian hamsters, whether such activation of
the immune system exacts energetic and reproductive costs,
and whether such costs vary seasonally. Male Siberian
hamsters were raised from birth in long (LD) or short days
(SD), which respectively initiate or inhibit the onset of
puberty. To elicit a specific immune response, hamsters were
injected with a novel antigen (keyhole limpet hemocyanin
[KLH]) as juveniles. Reproductive development was attenuated
and body temperature was elevated in LD hamsters relative to
saline-injected control animals. In contrast, KLH treatments
affected neither thermoregulation nor reproductive
development in photoinhibited SD hamsters. In experiment 2,
juvenile male hamsters were challenged with bacterial
lipopolysaccharide (LPS) in order to elicit an innate immune
response. Febrile and anorexic responses to LPS were greater
in reproductively stimulated LD hamsters relative to
reproductively inhibited SD hamsters. LPS treatments
attenuated somatic and testicular development in LD
hamsters, but did not significantly affect circulating
testosterone concentrations. In contrast, LPS treatments
were without effect on somatic and reproductive development
in SD hamsters. These experiments indicate that photoperiod
affects antigen-specific antibody production, febrile
responses to LPS, and sickness behaviors in juvenile
Siberian hamsters, and that peripubertal activation of the
immune system exacts energetic and metabolic costs that can
diminish the magnitude of somatic and reproductive
maturation in LD. The data also underscore the importance of
seasonally dependent life history factors in assessing
physiological tradeoffs.},
Doi = {10.1095/biolreprod.103.023408},
Key = {fds250849}
}
@article{fds197415,
Author = {SD Bilbo and RJ Nelson},
Title = {Photoperiod influences the effects of exercise and food
restriction on an antigen-specific immune response in
Siberian hamsters.},
Journal = {Endocrinology},
Volume = {145},
Number = {2},
Pages = {556-64},
Year = {2004},
Month = {February},
ISSN = {0013-7227},
url = {http://dx.doi.org/10.1210/en.2003-1035},
Keywords = {Animals • Antigens • Cricetinae • Eating
• Energy Metabolism • Food Deprivation* •
Hydrocortisone • Hypersensitivity, Delayed •
Immunity* • Male • Phodopus • Photoperiod*
• Physical Exertion • Reproduction • Seasons
• blood • immunology* • physiology*},
Abstract = {Environmental conditions influence the onset and severity of
illness and infection and may compromise survival.
Energetically challenging conditions during winter may
directly induce death through hypothermia, starvation, or
shock. The ability to forecast and prepare for the arrival
of challenging conditions associated with winter (e.g. low
temperatures, decreased food) likely confers survival
advantages. Siberian hamsters (Phodopus sungorus) stop
reproduction and reduce body mass (approximately 25%) during
short, winter-like day lengths, resulting in energetic
savings. Hamsters also increase circulating glucocorticoids
and lymphocytes (e.g. T cells, NK cells), and exhibit
enhanced antigen-specific delayed-type-hypersensitivity
(DTH) responses in the skin during short days (SDs). We
tested the hypothesis that Siberian hamsters use SD lengths
to signal the onset of winter to mediate the energetic
trade-offs among body mass, reproductive function, and
immune function. Long-day (LD; 16 h light, 8 h dark) and SD
(8 h light, 16 h dark) hamsters were either food restricted
(25%) or provided ad libitum (ad lib) food for 4 wk; half of
all hamsters in each food condition had voluntary access to
a running wheel, and half remained sedentary. SD hamsters
enhanced DTH responses compared with LD hamsters under
sedentary ad lib conditions. Exercise enhanced DTH in LD
hamsters regardless of food intake. Furthermore,
food-restriction did not significantly influence DTH in LD
hamsters. In contrast, food-restriction suppressed DTH in SD
hamsters regardless of activity condition, and exercise
modestly enhanced DTH only in SD hamsters with ad lib access
to food. In sum, moderate energetic deficiency suppressed
DTH in SD (but not LD) hamsters, and this suggests that
hamsters may have evolved to enhance immune responses during
winter in preparation for increased metabolic
stressors.},
Language = {eng},
Doi = {10.1210/en.2003-1035},
Key = {fds197415}
}
@article{fds250850,
Author = {Bilbo, SD and Nelson, RJ},
Title = {Photoperiod influences the effects of exercise and food
restriction on an antigen-specific immune response in
Siberian hamsters.},
Journal = {Endocrinology},
Volume = {145},
Number = {2},
Pages = {556-564},
Year = {2004},
Month = {February},
ISSN = {0013-7227},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14605007},
Abstract = {Environmental conditions influence the onset and severity of
illness and infection and may compromise survival.
Energetically challenging conditions during winter may
directly induce death through hypothermia, starvation, or
shock. The ability to forecast and prepare for the arrival
of challenging conditions associated with winter (e.g. low
temperatures, decreased food) likely confers survival
advantages. Siberian hamsters (Phodopus sungorus) stop
reproduction and reduce body mass (approximately 25%) during
short, winter-like day lengths, resulting in energetic
savings. Hamsters also increase circulating glucocorticoids
and lymphocytes (e.g. T cells, NK cells), and exhibit
enhanced antigen-specific delayed-type-hypersensitivity
(DTH) responses in the skin during short days (SDs). We
tested the hypothesis that Siberian hamsters use SD lengths
to signal the onset of winter to mediate the energetic
trade-offs among body mass, reproductive function, and
immune function. Long-day (LD; 16 h light, 8 h dark) and SD
(8 h light, 16 h dark) hamsters were either food restricted
(25%) or provided ad libitum (ad lib) food for 4 wk; half of
all hamsters in each food condition had voluntary access to
a running wheel, and half remained sedentary. SD hamsters
enhanced DTH responses compared with LD hamsters under
sedentary ad lib conditions. Exercise enhanced DTH in LD
hamsters regardless of food intake. Furthermore,
food-restriction did not significantly influence DTH in LD
hamsters. In contrast, food-restriction suppressed DTH in SD
hamsters regardless of activity condition, and exercise
modestly enhanced DTH only in SD hamsters with ad lib access
to food. In sum, moderate energetic deficiency suppressed
DTH in SD (but not LD) hamsters, and this suggests that
hamsters may have evolved to enhance immune responses during
winter in preparation for increased metabolic
stressors.},
Doi = {10.1210/en.2003-1035},
Key = {fds250850}
}
@article{fds197419,
Author = {BJ Prendergast and SD Bilbo and RJ Nelson},
Title = {Photoperiod controls the induction, retention, and retrieval
of antigen-specific immunological memory.},
Journal = {American journal of physiology. Regulatory, integrative and
comparative physiology},
Volume = {286},
Number = {1},
Pages = {R54-60},
Year = {2004},
Month = {January},
ISSN = {0363-6119},
url = {http://dx.doi.org/10.1152/ajpregu.00381.2003},
Keywords = {Animals • Antibody Formation • Cricetinae •
Dinitrofluorobenzene • Hemocyanin •
Hypersensitivity, Delayed • Immunization •
Immunologic Memory • Male • Phodopus •
Photoperiod* • Reproduction • immunology* •
physiology* • physiopathology • radiation effects
• radiation effects*},
Abstract = {Changes in day length affect several measures of immunity in
seasonally breeding mammals. In Siberian hamsters (Phodopus
sungorus), short day lengths suppress specific secondary
antibody responses to the keyhole limpet hemocyanin (KLH)
antigen and enhance cutaneous delayed-type hypersensitivity
(DTH) responses to dinitrofluorobenzene (DNFB). These
experiments tested whether day length affects secondary
antibody and DTH responses by altering immune function
solely during the interval after the initial exposure to
each antigen, solely during the interval after the second
exposure, or during both stages of the respective immune
responses. Adult male Siberian hamsters were exposed to
either a long (16 h light/day; LD) or a short (8 h
light/day; SD) photoperiod for 7.5 wk before receiving an
initial exposure to each antigen (KLH injection, cutaneous
DNFB treatment; separate groups of animals for each
antigen). A subset of LD hamsters was transferred to the SD
photo-period, and a subset of SD hamsters was transferred to
the LD photoperiod. Other hamsters remained in LD or SD.
Eight weeks later, all hamsters were challenged with a
second subcutaneous injection of KLH or a second application
of DNFB to the ear, and immune responses were measured.
Exposure to SD during the primary antibody response did not
affect secondary IgG responses, but SD exposure during the
secondary response significantly suppressed IgG production
independent of day length during the initial KLH treatment.
In contrast, exposure to SD during the DNFB challenge
enhanced the ensuing DTH response, but this enhancement
depended on the photoperiod prevailing during the initial
exposure. Exposure to SD during the sensitization stage did
not enhance DTH in hamsters subsequently exposed to LD. The
data suggest that short photoperiods have enduring effects
on immune responsiveness and on the establishment and
retention of immunological memory.},
Language = {eng},
Doi = {10.1152/ajpregu.00381.2003},
Key = {fds197419}
}
@article{fds250851,
Author = {Prendergast, BJ and Bilbo, SD and Nelson, RJ},
Title = {Photoperiod controls the induction, retention, and retrieval
of antigen-specific immunological memory.},
Journal = {American journal of physiology. Regulatory, integrative and
comparative physiology},
Volume = {286},
Number = {1},
Pages = {R54-R60},
Year = {2004},
Month = {January},
ISSN = {0363-6119},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12958060},
Abstract = {Changes in day length affect several measures of immunity in
seasonally breeding mammals. In Siberian hamsters (Phodopus
sungorus), short day lengths suppress specific secondary
antibody responses to the keyhole limpet hemocyanin (KLH)
antigen and enhance cutaneous delayed-type hypersensitivity
(DTH) responses to dinitrofluorobenzene (DNFB). These
experiments tested whether day length affects secondary
antibody and DTH responses by altering immune function
solely during the interval after the initial exposure to
each antigen, solely during the interval after the second
exposure, or during both stages of the respective immune
responses. Adult male Siberian hamsters were exposed to
either a long (16 h light/day; LD) or a short (8 h
light/day; SD) photoperiod for 7.5 wk before receiving an
initial exposure to each antigen (KLH injection, cutaneous
DNFB treatment; separate groups of animals for each
antigen). A subset of LD hamsters was transferred to the SD
photo-period, and a subset of SD hamsters was transferred to
the LD photoperiod. Other hamsters remained in LD or SD.
Eight weeks later, all hamsters were challenged with a
second subcutaneous injection of KLH or a second application
of DNFB to the ear, and immune responses were measured.
Exposure to SD during the primary antibody response did not
affect secondary IgG responses, but SD exposure during the
secondary response significantly suppressed IgG production
independent of day length during the initial KLH treatment.
In contrast, exposure to SD during the DNFB challenge
enhanced the ensuing DTH response, but this enhancement
depended on the photoperiod prevailing during the initial
exposure. Exposure to SD during the sensitization stage did
not enhance DTH in hamsters subsequently exposed to LD. The
data suggest that short photoperiods have enduring effects
on immune responsiveness and on the establishment and
retention of immunological memory.},
Doi = {10.1152/ajpregu.00381.2003},
Key = {fds250851}
}
@article{fds250816,
Author = {Bilbo, SD and Nelson, RJ},
Title = {Sex differences in photoperiodic and stress-induced
enhancement of immune function in Siberian
hamsters.},
Journal = {Brain, behavior, and immunity},
Volume = {17},
Number = {6},
Pages = {462-472},
Year = {2003},
Month = {December},
ISSN = {0889-1591},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14583238},
Keywords = {Adaptation, Physiological • Animals • Cricetinae
• Female • Gonadal Steroid Hormones •
Hydrocortisone • Hypersensitivity, Delayed • Male
• Phodopus • Photoperiod* • Reproduction
• Seasons • Sex Factors • Stress,
Physiological • blood • immunology •
immunology*},
Abstract = {Siberian hamsters breed during the long days of spring and
summer when environmental conditions (e.g., ambient
temperatures, food availability) are favorable for
reproduction. Environmental conditions may also influence
the onset and severity of infection and disease, and
photoperiodic alterations in immune function may comprise
part of a repertoire of seasonal adaptations to help survive
winter. In order to test the hypothesis that animals use day
length to anticipate seasonal stressors and adjust immune
function, we measured antigen-specific delayed-type-hypersensitivity
(DTH) responses in the skin of male and female hamsters
during long, "summer-like," or short, "winter-like" days, at
baseline and following acute restraint stress. Sex steroid
hormones were lower, and cortisol was higher, in males and
females during short days. Baseline DTH was enhanced in
short- compared to long-day males, and acute stress
augmented this effect. In contrast, photoperiod alone did
not influence the DTH response in females. As predicted,
female hamsters exhibited significantly higher DTH responses
than males during long days, but not during short days.
However, this enhancement was observed in acutely stressed
females only. Cortisol concentrations were significantly
higher at baseline in females, and increased more in
response to stress, compared to males in both photoperiods.
These results suggest that photoperiod provides a useful cue
by which stressors in the environment may be anticipated in
order to adjust immune function. Furthermore, interactions
among reproductive status and stress responses appear to
mediate the expression of sex differences in immune
responses in hamsters.},
Language = {eng},
Doi = {10.1016/s0889-1591(03)00063-1},
Key = {fds250816}
}
@article{fds250815,
Author = {Bilbo, SD and Dhabhar, FS and Viswanathan, K and Saul, A and Nelson,
RJ},
Title = {Photoperiod affects the expression of sex and species
differences in leukocyte number and leukocyte trafficking in
congeneric hamsters.},
Journal = {Psychoneuroendocrinology},
Volume = {28},
Number = {8},
Pages = {1027-1043},
Year = {2003},
Month = {November},
ISSN = {0306-4530},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14529706},
Keywords = {Animals • Cricetinae • Female •
Hydrocortisone • Immune System • Leukocyte Count
• Leukocytes • Male • Maternal Behavior
• Paternal Behavior • Phodopus • Photoperiod*
• Reproduction • Seasons • Sex
Characteristics • Species Specificity • Stress,
Physiological • blood* • immunology •
immunology* • physiology • physiology*},
Abstract = {Sex differences in immune function are well documented.
These sex differences may be modulated by social and
environmental factors. Individuals of polygynous species
generally exhibit more pronounced sex differences in immune
parameters than individuals of monogamous species, often
displaying an energetic trade-off between enhanced immunity
and high mating success. During winter, animals contend with
environmental conditions (e.g. low temperatures and
decreased food availability) that evoke energetic-stress
responses; many mammals restrict reproduction in response to
photoperiod as part of an annual winter coping strategy. To
test the hypothesis that extant sex and species differences
in immune surveillance may be modulated by photoperiod, we
examined leukocyte numbers in males and females of two
closely related hamster species (Phodopus). As predicted,
uniparental P. sungorus exhibited a robust sex difference,
with total white blood cells, total lymphocytes, T cells,
and B cells higher in females than males, during long days
when reproduction occurs, but not during short days when
reproduction usually stops. In contrast, biparental male and
female P. campbelli exhibited comparable leukocyte numbers
during both long and short days. To study sex differences in
stress responses, we also examined immune cell trafficking
in response to an acute (2 h) restraint stressor. During
stressful challenges, it appears beneficial for immune cells
to exit the blood and move to primary immune defense areas
such as the skin, in preparation for potential injury or
infection. Acute stress moved lymphocytes and monocytes out
of the blood in all animals. Blood cortisol concentrations
were increased in P. sungorus females compared to males at
baseline (52%) and in response to restraint stress (38%),
but only in long days. P. campbelli males and females
exhibited comparable blood cortisol and stress responses
during both long and short days. Our results suggest that
interactions among social factors and the environment play a
significant role in modulating sex and seasonal alterations
in leukocyte numbers and stress responses.},
Language = {eng},
Doi = {10.1016/s0306-4530(02)00122-1},
Key = {fds250815}
}
@article{fds250814,
Author = {Bilbo, SD and Quan, N and Prendergast, BJ and Bowers, SL and Nelson,
RJ},
Title = {Photoperiod alters the time course of brain cyclooxygenase-2
expression in Siberian hamsters.},
Journal = {Journal of neuroendocrinology},
Volume = {15},
Number = {10},
Pages = {958-964},
Year = {2003},
Month = {October},
ISSN = {0953-8194},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12969240},
Keywords = {Adjuvants, Immunologic • Animals • Body
Temperature • Body Weight • Brain •
Cricetinae • Cyclooxygenase 2 • Dinoprostone
• Endothelium, Vascular • Fever •
Immunohistochemistry • Isoenzymes •
Lipopolysaccharides • Male • Nerve Tissue Proteins
• Organ Size • Phodopus • Photoperiod* •
Preoptic Area • Prostaglandin-Endoperoxide Synthases
• RNA, Messenger • Radioimmunoassay • Testis
• Time Factors • biosynthesis • biosynthesis*
• chemically induced • cytology • drug
effects • enzymology* • metabolism •
physiology},
Abstract = {Fever is initiated by activation of the arachidonic acid
cascade and the biosynthesis of prostaglandins within the
brain. Inducible cyclooxygenase (COX-2) is a rate-limiting
enzyme in prostaglandin synthesis, and the number of blood
vessels expressing COX-2 correlates with elevated body
temperature following peripheral lipopolysaccharide (LPS).
Despite its importance in host defense, fever is
energetically expensive and we hypothesized that fever may
be limited by available metabolic resources. During winter,
when competing metabolic demands are constrained by low
temperatures and food availability, it was predicted that
fever duration would be reduced in seasonally breeding
Siberian hamsters (Phodopus sungorus). We measured
LPS-induced COX-2 expression in blood vessels of hamsters to
test whether photoperiodic alterations in fever duration are
centrally mediated, or whether they reflect changes in
peripheral modulation of body temperature. Hamsters housed
in long, 'summer-like' or short, 'winter-like' day lengths
for 10 weeks were injected with LPS, and brains were
collected 2, 4, or 8 h later. COX-2 expression was
comparably increased in long- and short-day hamsters by 2 h
and 4 h post-LPS; however, short-day hamsters exhibited
significantly fewer COX-2-positive cells and blood vessels
by 8 h post-LPS compared to long-day hamsters, corresponding
with reduced fever duration in short-day hamsters. Cortisol
concentrations increased more than two-fold in short-day
compared to long-day hamsters by 4 h; this increase may have
contributed to the decrease in COX-2 expression observed by
8 h in short days. We conclude that short photoperiods
significantly altered the time course of central COX-2
protein expression in hamsters in a manner consistent with
reduced fever duration.},
Language = {eng},
Doi = {10.1046/j.1365-2826.2003.01084.x},
Key = {fds250814}
}
@article{fds250813,
Author = {Bilbo, SD and Hotchkiss, AK and Chiavegatto, S and Nelson,
RJ},
Title = {Blunted stress responses in delayed type hypersensitivity in
mice lacking the neuronal isoform of nitric oxide
synthase.},
Journal = {Journal of neuroimmunology},
Volume = {140},
Number = {1-2},
Pages = {41-48},
Year = {2003},
Month = {July},
ISSN = {0165-5728},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12864970},
Keywords = {Animals • Behavior, Animal • Body Mass Index
• Corticosterone • Hypersensitivity, Delayed
• Immunosuppression • Isoenzymes • Male
• Mice • Mice, Inbred C57BL • Mice, Knockout
• Motor Activity • Nerve Tissue Proteins •
Neurons • Nitric Oxide Synthase • Nitric Oxide
Synthase Type I • Restraint, Physical • Stress,
Physiological • blood • deficiency •
deficiency* • enzymology* • genetics •
genetics* • immunology • physiology •
prevention & control},
Abstract = {Nitric oxide (NO) is implicated in inflammation and
hypothalamic-pituitary responses to immune stimuli; however,
the specific role of NO from neurons during stress-induced
immune responses remains unspecified. We measured
antigen-specific delayed-type-hypersensitivity (DTH)
responses in the skin of wild-type (WT) and neuronal nitric
oxide synthase knockout (nNOS(-/-)) mice at baseline and
after 2 h of restraint. Baseline corticosterone
concentrations were higher in nNOS(-/-) than WT mice.
However, stress-induced increases in corticosterone were
dampened in nNOS(-/-) mice, and restraint suppressed DTH
only in WT animals. Furthermore, WT mice lost more body mass
after stress, and exhibited more anxiety-like behavior in
the open field, than nNOS(-/-) mice. Neuronal NO appears to
be involved in the neuroendocrine-immune response to stress,
perhaps via glucocorticoid regulation.},
Language = {eng},
Doi = {10.1016/s0165-5728(03)00175-9},
Key = {fds250813}
}
@article{fds250812,
Author = {Prendergast, BJ and Hotchkiss, AK and Bilbo, SD and Kinsey, SG and Nelson, RJ},
Title = {Photoperiodic adjustments in immune function protect
Siberian hamsters from lethal endotoxemia.},
Journal = {Journal of biological rhythms},
Volume = {18},
Number = {1},
Pages = {51-62},
Year = {2003},
Month = {February},
ISSN = {0748-7304},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12568244},
Keywords = {Animals • Body Weight • Cell Division •
Cricetinae • Cytokines • Endotoxins • Female
• Immunity, Cellular • Lethal Dose 50 •
Lymphocytes • Macrophages • Male • Organ Size
• Phodopus • Photoperiod* • Sex
Characteristics • Shock, Septic • Spleen •
Survival Analysis • Testis • Tumor Necrosis
Factor-alpha • biosynthesis • chemistry •
drug effects • immunology • metabolism •
physiology • physiology* • physiopathology •
toxicity*},
Abstract = {Seasonal changes in day length enhance or suppress
components of immune function in individuals of several
mammalian species. Siberian hamsters (Phodopus sungorus)
exhibit multiple changes in neuroendocrine, reproductive,
and immune function after exposure to short days. The manner
in which these changes are integrated into the host response
to pathogens is not well understood. The present experiments
tested the hypothesis that short-day changes in immune
function alter the pathogenesis of septic shock and survival
after challenge with endotoxin. Male and female Siberian
hamsters raised in long-day photoperiods were transferred as
adults to short days or remained in their natal photoperiod.
Six to 8 weeks later, hamsters were injected i.p. with 0, 1,
2.5, 10, 25, or 50 mg/kg bacterial lipopolysaccharide (LPS)
(the biologically active constituent of endotoxin), and
survival was monitored for 96 h. Short days significantly
improved survival of male hamsters treated with 10 or 25
mg/kg LPS and improved survival in females treated with 50
mg/kg LPS. Transfer from long to short days shifted the LD50
in males by approximately 90%, from 5.3 to 9.9 mg/kg, and in
females from 11.1 to 15.0 mg/kg (+35%). Long-day females
were more resistant than were males to lethal endotoxemia.
In vitro production of the proinflammatory cytokine TNFalpha
in response to LPS stimulation was significantly lower in
macrophages extracted from short-day relative to long-day
hamsters, as were circulating concentrations of TNFalpha in
vivo after i.p. administration of LPS, suggesting that
diminished cytokine responses to LPS in short days may
mitigate the lethality of endotoxemia. Adaptation to short
days induces changes in immune parameters that affect
survival in the face of immune challenges.},
Language = {eng},
Doi = {10.1177/0748730402239676},
Key = {fds250812}
}
@article{fds69264,
Author = {Bilbo, SD and Hotchkiss, AH and Chiavegatto, S and Nelson,
RJ},
Title = {Blunted stress responses in delayed type hypersensitivity in
mice lacking the neuronal isoform of nitric oxide
synthase},
Journal = {Journal of Neuroimmunology},
Volume = {140},
Pages = {41-48},
Year = {2003},
Key = {fds69264}
}
@article{fds69266,
Author = {Bilbo, SD and Dhabhar, FS and Viswanathan, K and Light, A and Nelson,
RJ},
Title = {Photoperiod affects the expression of sex and species
differences in leukocyte number and leukocyte trafficking of
congeneric hamsters},
Journal = {Psychoneuroendocrinology},
Volume = {28},
Number = {8},
Pages = {1027-1043},
Year = {2003},
Key = {fds69266}
}
@article{fds250810,
Author = {Bilbo, SD and Nelson, RJ},
Title = {Melatonin regulates energy balance and attenuates fever in
Siberian hamsters.},
Journal = {Endocrinology},
Volume = {143},
Number = {7},
Pages = {2527-2533},
Year = {2002},
Month = {July},
ISSN = {0013-7227},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12072384},
Abstract = {Fever is considered an important host defense response but
requires significant metabolic energy. During winter many
animals must balance immune function with competing
physiological demands (i.e. thermoregulation) to survive.
Winterlike patterns of melatonin secretion induce a number
of energy-saving adaptations. For instance, Siberian
hamsters attenuate the duration of fever during simulated
short winter day lengths, presumably to conserve energy. To
determine the proximate role of melatonin in mediating this
photoperiodic response, hamsters housed in long days were
injected with saline or melatonin 4 h before lights off for
either 1 or 6 wk and assessed for fever following injections
of bacterial lipopolysaccharide. Fever duration was
attenuated (32%) only in hamsters that decreased body mass,
increased cortisol, and exhibited gonadal regression in
response to 6 wk of melatonin. Because melatonin-treated
hamsters lost significant body mass, fever was assessed in a
second long-day group following ad libitum food intake, food
restriction, or 24-h food deprivation. Food restriction
sufficient to reduce body mass by approximately 25%, but not
to reduce leptin, did not influence fever, and 24-h food
deprivation virtually abolished fever. Our data suggest that
long-term exposure to long-duration melatonin signals is
required to induce the physiological changes necessary for
short-day immune responses, perhaps involving interactions
with hormones such as cortisol and leptin.},
Doi = {10.1210/endo.143.7.8922},
Key = {fds250810}
}
@article{fds250809,
Author = {Bilbo, SD and Drazen, DL and Quan, N and He, L and Nelson,
RJ},
Title = {Short day lengths attenuate the symptoms of infection in
Siberian hamsters.},
Journal = {Proceedings. Biological sciences},
Volume = {269},
Number = {1490},
Pages = {447-454},
Year = {2002},
Month = {March},
ISSN = {0962-8452},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11886635},
Abstract = {Symptoms of infection, such as fever, anorexia and lethargy,
are ubiquitous among vertebrates. Rather than nonspecific
manifestations of illness, these responses are organized,
adaptive strategies that are often critical to host
survival. During times of energetic shortage such as winter,
however, it may be detrimental for individuals to prolong
energetically demanding symptoms such as fever. Individuals
may adjust their immune responses prior to winter by using
day length to anticipate energetically-demanding conditions.
If the expression of sickness behaviours is constrained by
energy availability, then cytokine production, fever, and
anorexia should be attenuated in infected Siberian hamsters
housed under simulated winter photoperiods. We housed
hamsters in either long (14 L : 10 D) or short (10 L : 14 D)
day lengths and assessed cytokines, anorexia and fever
following injections of lipopolysaccharide (LPS). Short days
attenuated the response to lipopolysaccharide, by decreasing
the production of interleukin (IL)-6 and IL-1beta, and
diminishing the duration of fever and anorexia. Short-day
exposure in hamsters also decreased the ingestion of dietary
iron, a nutrient vital to bacterial replication. Taken
together, short day lengths attenuated the symptoms of
infection, presumably to optimize energy expenditure and
survival outcome.},
Doi = {10.1098/rspb.2001.1915},
Key = {fds250809}
}
@article{fds250811,
Author = {Bilbo, SD and Dhabhar, FS and Viswanathan, K and Saul, A and Yellon, SM and Nelson, RJ},
Title = {Short day lengths augment stress-induced leukocyte
trafficking and stress-induced enhancement of skin immune
function.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {99},
Number = {6},
Pages = {4067-4072},
Year = {2002},
Month = {March},
ISSN = {0027-8424},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11904451},
Abstract = {Environmental conditions influence the onset and severity of
infection and disease. Stressful conditions during winter
may weaken immune function and further compromise survival
by means of hypothermia, starvation, or shock. To test the
hypothesis that animals may use photoperiod to anticipate
the onset of seasonal stressors and adjust immune function,
we evaluated glucocorticoids and the distribution of blood
leukocytes in Siberian hamsters (Phodopus sungorus) exposed
to long day lengths (i.e., summer) or short day (SD) lengths
(i.e., winter) at baseline and during acute stress. We also
investigated the influence of photoperiod and acute stress
on a delayed-type hypersensitivity response in the skin. SDs
increased glucocorticoid concentrations and the absolute
number of circulating blood leukocytes, lymphocytes, T
cells, and natural killer cells at baseline in hamsters.
During stressful challenges, it appears beneficial for
immune cells to exit the blood and move to primary immune
defense areas such as the skin, in preparation for potential
injury or infection. Acute (2 h) restraint stress induced
trafficking of lymphocytes and monocytes out of the blood.
This trafficking occurred more rapidly in SDs compared to
long days. Baseline delayed-type hypersensitivity responses
were enhanced during SDs; this effect was augmented by acute
stress and likely reflected more rapid redistribution of
leukocytes out of the blood and into the skin. These results
suggest that photoperiod may provide a useful cue by which
stressors in the environment may be anticipated to adjust
the repertoire of available immune cells and increase
survival likelihood.},
Doi = {10.1073/pnas.062001899},
Key = {fds250811}
}
@article{fds250803,
Author = {Drazen, DL and Bilu, D and Bilbo, SD and Nelson, RJ},
Title = {Melatonin enhancement of splenocyte proliferation is
attenuated by luzindole, a melatonin receptor
antagonist.},
Journal = {American journal of physiology. Regulatory, integrative and
comparative physiology},
Volume = {280},
Number = {5},
Pages = {R1476-R1482},
Year = {2001},
Month = {May},
ISSN = {0363-6119},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11294771},
Abstract = {In addition to marked seasonal changes in reproductive,
metabolic, and other physiological functions, many
vertebrate species undergo seasonal changes in immune
function. Despite growing evidence that photoperiod mediates
seasonal changes in immune function, little is known
regarding the neuroendocrine mechanisms underlying these
changes. Increased immunity in short days is hypothesized to
be due to the increase in the duration of nightly melatonin
secretion, and recent studies indicate that melatonin acts
directly on immune cells to enhance immune parameters. The
present study examined the contribution of melatonin
receptors in mediating the enhancement of splenocyte
proliferation in response to the T cell mitogen Concanavalin
A in mice. The administration of luzindole, a high-affinity
melatonin receptor antagonist, either in vitro or in vivo
significantly attenuated the ability of in vitro melatonin
to enhance splenic lymphocyte proliferation during the day
or night. In the absence of melatonin or luzindole,
splenocyte proliferation was intrinsically higher during the
night than during the day. In the absence of melatonin
administration, luzindole reduced the ability of spleen
cells to proliferate during the night, when endogenous
melatonin concentrations are naturally high. This effect was
not observed during the day, when melatonin concentrations
are low. Taken together, these results suggest that
melatonin enhancement of splenocyte proliferation is
mediated directly by melatonin receptors on splenocytes and
that there is diurnal variation in splenocyte proliferation
in mice that is also mediated by splenic melatonin
receptors.},
Doi = {10.1152/ajpregu.2001.280.5.r1476},
Key = {fds250803}
}
@article{fds250802,
Author = {Bilbo, SD and Nelson, RJ},
Title = {Sex steroid hormones enhance immune function in male and
female Siberian hamsters.},
Journal = {American journal of physiology. Regulatory, integrative and
comparative physiology},
Volume = {280},
Number = {1},
Pages = {R207-R213},
Year = {2001},
Month = {January},
ISSN = {0363-6119},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11124153},
Abstract = {Immune function is better in females than in males of many
vertebrate species, and this dimorphism has been attributed
to the presence of immunosuppressive androgens in males. We
investigated the influence of sex steroid hormones on immune
function in male and female Siberian hamsters. Previous
studies indicated that immune function was impaired in male
and female hamsters housed under short-day photoperiods when
androgen and estrogen concentrations were virtually
undetectable. In experiment 1, animals were gonadally
intact, gonadectomized (gx), or gx with hormone replacement.
Females exhibited the expected increase in antibody
production over males, independent of hormone treatment
condition, whereas male and female gx animals exhibited
decreased lymphocyte proliferation to the T cell mitogen,
phytohemagglutinin (PHA) compared with intact animals, and
this effect was reversed in gx hamsters following
testosterone and estradiol treatment, respectively. In
experiment 2, testosterone, dihydrotestosterone, and
estradiol all enhanced cell-mediated immunity in vitro,
suggesting that sex steroid hormones may be enhancing immune
function through direct actions on immune cells. In
experiment 3, an acute mitogen challenge of
lipopolysaccharide significantly suppressed lymphocyte
proliferation to PHA in intact males but not females,
suggesting that males may be less reactive to a subsequent
mitogenic challenge than females. Contrary to evidence in
many species such as rats, mice, and humans, these data
suggest that sex steroid hormones enhance immunity in both
male and female Siberian hamsters.},
Doi = {10.1152/ajpregu.2001.280.1.r207},
Key = {fds250802}
}
@article{fds250807,
Author = {Bilbo, SD and Nelson, RJ},
Title = {Behavioral phenotyping of transgenic and knockout animals: a
cautionary tale.},
Journal = {Lab animal},
Volume = {30},
Number = {1},
Pages = {24-29},
Year = {2001},
Month = {January},
ISSN = {0093-7355},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11385723},
Abstract = {Knockout and transgenic mice are extremely useful for
behavioral research, especially for linking specific genes
with behaviors. The authors present caveats to be aware of
when using such mice in research situations.},
Key = {fds250807}
}
@article{fds250805,
Author = {Bilbo, SD and Day, LB and Wilczynski, W},
Title = {Anticholinergic effects in frogs in a Morris water maze
analog.},
Journal = {Physiology & behavior},
Volume = {69},
Number = {3},
Pages = {351-357},
Year = {2000},
Month = {May},
ISSN = {0031-9384},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10869602},
Abstract = {We determined the effect of two doses of the centrally
acting anticholinergic drug, atropine sulfate (AS), on the
performance of female Northern Leopard frogs (Rana pipiens)
in a visual cue analog of the Morris water task. Untreated
frogs learned the visually cued task, while frogs treated
with 150 mg/kg AS were significantly slower than controls in
learning to escape warm water by finding a visible platform,
and there was a dose-dependent response, with frogs treated
with 50 mg/kg AS performing midway between the higher dose
and control frogs. These results suggest that the general
role of the cholinergic system in learning is important in
amphibians, and that this role is evolutionarily conserved
across vertebrate species.},
Doi = {10.1016/s0031-9384(99)00251-6},
Key = {fds250805}
}
@article{fds250804,
Author = {Bilbo, SD and Klein, SL and DeVries, AC and Nelson,
RJ},
Title = {Lipopolysaccharide facilitates partner preference behaviors
in female prairie voles.},
Journal = {Physiology & behavior},
Volume = {68},
Number = {1-2},
Pages = {151-156},
Year = {1999},
Month = {December},
ISSN = {0031-9384},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10627074},
Abstract = {Exposure to proinflammatory cytokines (e.g., IL-1beta) or
lipopolysaccharide (LPS) produces an acute activation of the
immune response and results in a repertoire of behavioral
patterns collectively termed sickness behaviors. Although
nonspecific responses to pathogenic infection have
traditionally been viewed as maladaptive effects of
infection, sickness behaviors may have significant, adaptive
value for the host. One set of adaptive behaviors affected
by infection among mammals and birds is mate choice. In
Experiment 1, female prairie voles exhibited the expected
increase in blood corticosterone concentrations in response
to a 0.1 cc i.p. LPS injection (50 microg), indicating
activation of the endocrine system. A separate cohort of
females was injected with LPS or saline and paired for 6 h
with a novel, previously unpaired male. Following the
cohabitation period, LPS-injected females spent
significantly more time (p < 0.05) with the familiar partner
when given a choice between familiar and unfamiliar males in
a three-chamber apparatus designed to test partner
preferences. Saline-injected females spent significantly
more time with the unfamiliar male. In Experiment 2, males
injected with LPS or saline spent equal amounts of time with
familiar and unfamiliar females following a 6 h cohabitation
with a naive female, and therefore, did not exhibit
preferences. From a proximate perspective, this study
provides evidence that sickness behaviors influence female,
but not male, partner preference in prairie
voles.},
Doi = {10.1016/s0031-9384(99)00154-7},
Key = {fds250804}
}
%% Books
@book{fds198766,
Author = {J.M. Schwarz and S.D. Bilbo},
Title = {The Immune System and the Developing Brain},
Series = {McCarthy's The Developing Brain Series},
Publisher = {Morgan and Claypool Life Sciences},
Year = {2011},
Key = {fds198766}
}
%% Chapters in Books
@misc{fds362983,
Author = {Delage, C and Rendina, DN and Malacon, KE and Tremblay, MÈ and Bilbo,
SD},
Title = {Sex differences in microglia as a risk factor for
Alzheimer’s disease},
Pages = {79-104},
Booktitle = {Sex and Gender Differences in Alzheimer’s
Disease},
Year = {2021},
Month = {January},
ISBN = {9780128193440},
url = {http://dx.doi.org/10.1016/B978-0-12-819344-0.00008-9},
Abstract = {Women are known to have a significantly higher lifetime risk
of developing Alzheimer’s disease (AD) and recent research
shows that they also appear to suffer greater cognitive
deterioration than men at the same disease stage. However,
the exact mechanisms underlying this prevalence remain
elusive. The purpose of this review is to examine the
potential role of neuroinflammation and microglia in driving
this sex difference in AD. We first introduce the dual role
of microglia in AD, describing their transition from being
neuroprotective, in reducing amyloid burden during earlier
stages of disease, to their pathological role in
exacerbating tau pathology in the later stages. We then
describe sex differences in the immune system and in
microglial maturation and activities as well as how immune
activation in early life may modulate brain function later
in life. Lastly, sex differences in microglial function are
described in the contexts of aging and AD among other
neurodegenerative conditions.},
Doi = {10.1016/B978-0-12-819344-0.00008-9},
Key = {fds362983}
}
@misc{fds198784,
Author = {J.M. Schwarz and S.D. Bilbo},
Title = {Chapter 15: Microglia and Neurodevelopment},
Booktitle = {The Wiley-Blackwell Handbook of Psychoneuroimmunology},
Publisher = {Wiley-Blackwell},
Editor = {Kusnecov and Anisman},
Year = {2013},
Month = {December},
Key = {fds198784}
}
@misc{fds365186,
Author = {Schwarz, JM and Bilbo, SD},
Title = {Microglia and Neurodevelopment: Programming of Cognition
throughout the Lifespan},
Pages = {296-312},
Booktitle = {The Wiley-Blackwell Handbook of Psychoneuroimmunology},
Year = {2013},
Month = {January},
ISBN = {9781119979517},
url = {http://dx.doi.org/10.1002/9781118314814.ch15},
Abstract = {Neuroimmune activation during prenatal or early postnatal
development can have profound and long-lasting effects on
the brain. This chapter provides an up-to-date review of the
long-term effects of early-life immune activation on adult
cognition, a current perspective on the long-term mechanisms
by which these effects are propagated from development to
adulthood, and a brief primer on the techniques and
methodology by which the long-term consequences of
early-life immune activation on later-life cognition can be
investigated in a rodent model. The concept of perinatal
programming of the immune system and the potential effects
on brain and behavior in adulthood remains relatively
unexplored, despite strong evidence that perinatal exposure
to infectious agents has a number of influences on later
life outcomes including disease susceptibility, and,
increased vulnerability to cognitive and/or neuropsychiatric
disorders. A minor yet significant shift in microglial
function has significant negative consequences for
cognition.},
Doi = {10.1002/9781118314814.ch15},
Key = {fds365186}
}
%% Articles Submitted
@article{fds220606,
Author = {L.L. Williamson and S.D. Bilbo},
Title = {Neonatal infection modulates behavioral accuracy and
hippocampal activation on a Morris Water Maze
task},
Journal = {Physiology & Behavior},
Year = {2013},
Key = {fds220606}
}
%% Other
@misc{fds69283,
Author = {Spataro, LE and Walsh, MG and Levkoff, LH and Wieseler Frank and JL, Frank and MG, Bilbo and SD, Martin and TJ, Maier and SF and Watkins,
LR},
Title = {Laparotomy sensitizes dorsal spinal cord glia: Enhanced
glial response to later challenge},
Journal = {Society for Neuroscience Abstracts},
Year = {2004},
Key = {fds69283}
}
@misc{fds69284,
Author = {Neigh, GN and Bilbo, SD and Glasper, ER and DeVries,
AC},
Title = {Cardiac arrest/cardiopulmonary resuscitation increases the
delayed-type-hypersensitivity response and alters
hypothalamic-pituitary adrenal axis activity},
Journal = {PsychoNeuroImmunology Research Society Abstracts},
Year = {2004},
Key = {fds69284}
}
@misc{fds69281,
Author = {Bilbo, SD and Levkoff, LH and Mahoney, JH and Rudy, JW and Watkins, LR and Maier, SF},
Title = {Neonatal infection induces memory impairments and cytokine
alterations following an immune challenge in
adulthood},
Journal = {PsychoNeuroImmunology Research Society Abstracts},
Year = {2004},
Key = {fds69281}
}
@misc{fds69282,
Author = {Bilbo, SD and Mahoney, JH and Rudy, JW and Watkins, LR and Maier,
SF},
Title = {Neonatal infection alters hippocampal glia and induces
memory impairments and cytokine alterations following an
immune challenge in adulthood},
Journal = {Society for Neuroscience Abstracts},
Year = {2004},
Key = {fds69282}
}
@misc{fds69285,
Author = {Bilbo, SD and Dhabhar, FS and Viswanathan, K and Prendergast, BJ and Nelson, RJ},
Title = {Sex differences in photoperiodic and stress-induced
enhancement of immune function in Siberian
hamsters},
Journal = {PsychoNeuroImmunology Research Society Abstracts},
Year = {2003},
Key = {fds69285}
}
@misc{fds69286,
Author = {Bilbo, SD and Nelson, RJ},
Title = {Photoperiod and exercise affect metabolism and delayed type
hypersensitivity in Siberian hamsters},
Journal = {Society for Behavioral Neuroendocrinology
Abstracts},
Year = {2003},
Key = {fds69286}
}
@misc{fds69287,
Author = {Bowers, SL and Bilbo, SD and Nelson, RJ},
Title = {A comparison of chronic stressors effects on delayed type
hypersensitivity in mice},
Journal = {Society for Behavioral Neuroendocrinology
Abstracts},
Year = {2003},
Key = {fds69287}
}
@misc{fds69288,
Author = {Bilbo, SD and Neigh, GN and Glasper, ER and DeVries,
AC},
Title = {Enhanced delayed-type-hypersensitivity responses in cardiac
arrest survivors},
Journal = {Society for Neuroscience Abstracts},
Year = {2003},
Key = {fds69288}
}
@misc{fds69289,
Author = {Prendergast, BJ and Bilbo, SD and Nelson, RJ},
Title = {Day length regulates induction, retention, and retrieval of
immunological memory in Siberian hamsters},
Journal = {Society for Neuroscience Abstracts},
Year = {2003},
Key = {fds69289}
}
@misc{fds69291,
Author = {Viswanathan, K and Bilbo, SD and Dhabhar, FS},
Title = {Acute stress administered before primary immunization or
before challenge enhances skin delayed type hypersensitivity
responses to keyhole limpet hemocyanin (KLH)},
Journal = {PsychoNeuroImmunology Research Society Abstracts},
Year = {2002},
Key = {fds69291}
}
@misc{fds69293,
Author = {Neigh-McCandless, G and Bilbo, SD and Hotchkiss, AH and Nelson,
RJ},
Title = {Pyruvate supplementation attenuates stress-evoked
immunosuppression},
Journal = {Society for Behavioral Neuroendocrinology
Abstracts},
Year = {2002},
Key = {fds69293}
}
@misc{fds69294,
Author = {Hotchkiss, AK and Prendergast, BJ and Bilbo, SD and Nelson,
RJ},
Title = {Reproductive costs of immune system activation in juvenile
Siberian hamsters},
Journal = {Society for Behavioral Neuroendocrinology
Abstracts},
Year = {2002},
Key = {fds69294}
}
@misc{fds69295,
Author = {Bilbo, SD and Dhabhar, FS and Viswanathan, K and Light, A and Nelson,
RJ},
Title = {Sex and photoperiodic differences in immune function and
stress responses in congeneric hamsters},
Journal = {Society for Neuroscience Abstracts},
Year = {2002},
Key = {fds69295}
}
@misc{fds69296,
Author = {Neigh-McCandless, G and Bilbo, SD and Hotchkiss, AH and Nelson,
RJ},
Title = {Pyruvate supplementation ameliorates the effects of chronic
stress on immune and endocrine systems},
Journal = {Society for Neuroscience Abstracts},
Year = {2002},
Key = {fds69296}
}
@misc{fds69297,
Author = {Prendergast, BJ and Hotchkiss, AK and Bilbo, SD and Nelson,
RJ},
Title = {Circadian and photoperiodic control of immune function in
juvenile Siberian hamsters},
Journal = {Society for Neuroscience Abstracts},
Year = {2002},
Key = {fds69297}
}
@misc{fds69298,
Author = {Bilbo, SD and Dhabhar, FS and Yellon, SM and Nelson
RJ},
Title = {Photoperiodic and stress-induced changes in blood and
splenic leukocyte distributions in Siberian
hamsters},
Journal = {Society for Neuroscience Abstracts},
Year = {2001},
Key = {fds69298}
}
@misc{fds69299,
Author = {Bilbo, SD and Nelson, RJ},
Title = {Photoperiod affects immune function and sickness behavior in
Siberian hamsters},
Journal = {Society for Research on Biological Rhythms
Abstracts},
Year = {2000},
Key = {fds69299}
}
@misc{fds69300,
Author = {Drazen, DL and Bilbo, SD and Nelson, RJ},
Title = {In vitro melatonin enhancement of splenocyte proliferation
appears to be mediated directly by melatonin receptor
subtype 1B},
Journal = {Society for Behavioral Neuroendocrinology
Abstracts},
Year = {2000},
Key = {fds69300}
}
@misc{fds69301,
Author = {Bilbo, SD and Drazen, DL and Nelson, RJ},
Title = {Sickness behavior and energy balance vary as a function of
photoperiod in Siberian hamsters},
Journal = {Society for Neuroscience Abstracts},
Year = {2000},
Key = {fds69301}
}
@misc{fds69302,
Author = {Bilbo, SD and Drazen, DL and Bilu, D and Nelson,
RJ},
Title = {Luzindole attenuates the in vitro melatonin enhancement of
cell-mediated immunity in C57BL/6J house
mice},
Journal = {Society for Neuroscience Abstracts},
Year = {1999},
Key = {fds69302}
}
@misc{fds69303,
Author = {Bilbo, SD and Klein, SL and DeVries, AC and Nelson,
RJ},
Title = {Lipopolysaccharide elicits sexually dimorphic partner
preference behaviors in monogamous prairie
voles},
Journal = {Society for Behavioral Neuroendocrinology
Abstracts},
Year = {1999},
Key = {fds69303}
}
@misc{fds69304,
Author = {Bilbo, SD and Day, LB and Wilczynski, W},
Title = {An anticholinergic disrupts operant conditioning but not
spatial memory in frogs},
Journal = {Society for Neuroethology Abstracts},
Year = {1998},
Key = {fds69304}
}
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