Scholars@Duke
Staci D. Bilbo

Staci D. Bilbo

Haley Family Professor of Psychology and Neuroscience
Psychology & Neuroscience
staci.bilbo@duke.edu
GSRB II Rm 3016, Box 91050, Durham, NC 27708-0086
GSRB II Rm 3016, Box 91050, Durham, NC 27708

Selected Publications

Microglial MyD88-dependent pathways are regulated in a sex-specific manner in the context of HMGB1-induced anxiety.

Journal Article bioRxiv · July 1, 2024 Chronic stress is a significant risk factor for the development and recurrence of anxiety disorders. Chronic stress impacts the immune system, causing microglial functional alterations in the medial prefrontal cortex (mPFC), a brain region involved in the ... Full text Link to item Cite

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity.

Journal Article Cell reports · June 2024 Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting feta ... Full text Cite

Neuron Derived Cytokine Interleukin-34 Controls Developmental Microglia Function.

Journal Article bioRxiv · May 10, 2024 Neuron-microglia interactions dictate the development of neuronal circuits in the brain. However, the factors that support and broadly regulate these processes across developmental stages are largely unknown. Here, we find that IL34, a neuron-derived cytok ... Full text Link to item Cite

Gonadal hormones impart male-biased behavioral vulnerabilities to immune activation via microglial mitochondrial function.

Journal Article Brain, behavior, and immunity · January 2024 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 ... Full text Cite

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity.

Journal Article bioRxiv · December 19, 2023 Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting feta ... Full text Link to item Cite

Microbial modulation via cross-fostering prevents the effects of pervasive environmental stressors on microglia and social behavior, but not the dopamine system.

Journal Article Molecular psychiatry · June 2023 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 str ... Full text Cite

Microbial modulation prevents the effects of pervasive environmental stressors on microglia and social behavior, but not the dopamine system.

Journal Article Res Sq · February 9, 2023 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 str ... Full text Link to item Cite

Protocol to measure endotoxin from opaque tissues in mice using an optimized kinetic limulus amebocyte lysate assay.

Journal Article STAR protocols · December 2022 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 accumul ... Full text Cite

Maternal diet disrupts the placenta-brain axis in a sex-specific manner.

Journal Article Nat Metab · December 2022 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 develop ... Full text Link to item Cite

β-Endorphin mediates radiation therapy fatigue.

Journal Article Science advances · December 2022 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 ski ... Full text Cite

Microglia states and nomenclature: A field at its crossroads.

Journal Article Neuron · November 2022 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 t ... Full text Cite

Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring.

Journal Article Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · September 2022 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. H ... Full text Cite

Prenatal environmental stressors impair postnatal microglia function and adult behavior in males.

Journal Article Cell Rep · August 2, 2022 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 envi ... Full text Link to item Cite

Dietary fat: a potent microglial influencer.

Journal Article Trends in endocrinology and metabolism: TEM · March 2022 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 diabete ... Full text Cite

Microglia and Sensitive Periods in Brain Development.

Journal Article Current topics in behavioral neurosciences · January 2022 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, allo ... Full text Cite

Targeting Tau Mitigates Mitochondrial Fragmentation and Oxidative Stress in Amyotrophic Lateral Sclerosis.

Journal Article Molecular neurobiology · January 2022 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 Alz ... Full text Cite

Sickness and the Social Brain: How the Immune System Regulates Behavior across Species.

Journal Article Brain, behavior and evolution · January 2022 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. ... Full text Open Access Cite

Maternal diet disrupts the placenta-brain axis in a sex-specific manner

Journal Article · November 13, 2021 SUMMARYHigh 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. autis ... Full text Cite

Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses.

Journal Article Sci Transl Med · October 27, 2021 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 a ... Full text Open Access Link to item Cite

Morphine exposure alters Fos expression in a sex-, age-, and brain region-specific manner during adolescence.

Journal Article Developmental psychobiology · September 2021 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 ... Full text Cite

Primetime for microglia: When stress and infection collide.

Journal Article Neuron · August 2021 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 neur ... Full text Cite

Associations between maternal obesity, gestational cytokine levels and child obesity in the NEST cohort.

Journal Article Pediatr Obes · July 2021 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 ... Full text Link to item Cite

Vitamin D deficiency exacerbates UV/endorphin and opioid addiction.

Journal Article Science advances · June 2021 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 a ... Full text Cite

Sexually dimorphic placental responses to maternal SARS-CoV-2 infection.

Journal Article bioRxiv · March 29, 2021 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 ... Full text Link to item Cite

Sickness and the Social Brain: Love in the Time of COVID.

Journal Article Frontiers in psychiatry · January 2021 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, anxi ... Full text Cite

Sex differences in microglia as a risk factor for Alzheimer’s disease

Chapter · January 1, 2021 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 ... Full text Cite

Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number.

Journal Article Brain, behavior, and immunity · November 2020 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 developme ... Full text Cite

Sex-dependent neurobiological features of prenatal immune activation via TLR7.

Journal Article Molecular psychiatry · October 2020 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 cla ... Full text Cite

Microglia and sexual differentiation of the developing brain: A focus on ontogeny and intrinsic factors.

Journal Article Glia · June 2020 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 intricatel ... Full text Cite

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease.

Journal Article Neuropsychopharmacology · June 2020 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. Interes ... Full text Open Access Link to item Cite

Isolation of Microglia from Mouse or Human Tissue.

Journal Article STAR protocols · June 2020 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 dyna ... Full text Cite

Stressed-Out T Cells Fragment the Mind.

Journal Article Trends in immunology · February 2020 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 accumulatio ... Full text Cite

Placental Macrophages: A Window Into Fetal Microglial Function in Maternal Obesity.

Journal Article International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · October 2019 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 microgli ... Full text Cite

The inflammatory event of birth: How oxytocin signaling may guide the development of the brain and gastrointestinal system.

Journal Article Frontiers in neuroendocrinology · October 2019 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 mot ... Full text Cite

Mitochondria, Oxytocin, and Vasopressin: Unfolding the Inflammatory Protein Response.

Journal Article Neurotoxicity research · August 2019 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 r ... Full text Cite

A Protocol for Sedation Free MRI and PET Imaging in Adults with Autism Spectrum Disorder.

Journal Article Journal of autism and developmental disorders · July 2019 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 intera ... Full text Cite

Neuro-Immune Mechanisms Regulating Social Behavior: Dopamine as Mediator?

Journal Article Trends in neurosciences · May 2019 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 alt ... Full text Cite

Microglia Sculpt Sex Differences in Social Behavior.

Journal Article Neuron · April 2019 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 amy ... Full text Cite

Removal of microglial-specific MyD88 signaling alters dentate gyrus doublecortin and enhances opioid addiction-like behaviors.

Journal Article Brain Behav Immun · February 2019 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 functio ... Full text Link to item Cite

Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities.

Journal Article Immunity · February 2019 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 re ... Full text Cite

Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model.

Journal Article Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · January 2019 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 mode ... Full text Cite

Microglial dopamine receptor elimination defines sex-specific nucleus accumbens development and social behavior in adolescent rats.

Journal Article Nature communications · September 2018 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, b ... Full text Cite

The diverse culinary habits of microglia.

Journal Article Nature neuroscience · August 2018 Full text Cite

Gut-immune-brain dysfunction in Autism: Importance of sex.

Journal Article Brain research · August 2018 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, ga ... Full text Cite

Associations between maternal cytokine levels during gestation and measures of child cognitive abilities and executive functioning.

Journal Article Brain Behav Immun · May 2018 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 g ... Full text Link to item Cite

Sex Differences Shape Brain Development and Function, in Health and Disease: Policy Implications

Journal Article Policy Insights from the Behavioral and Brain Sciences · March 1, 2018 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 ... Full text Cite

Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders.

Journal Article Experimental neurology · January 2018 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 du ... Full text Cite

Environment matters: microglia function and dysfunction in a changing world.

Journal Article Current opinion in neurobiology · December 2017 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 ye ... Full text Cite

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 Article Neuropsychopharmacology · October 2017 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 sho ... Full text Open Access Link to item Cite

Perinatal western-type diet and associated gestational weight gain alter postpartum maternal mood.

Journal Article Brain Behav · October 2017 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 ... Full text Link to item Cite

Generation of a microglial developmental index in mice and in humans reveals a sex difference in maturation and immune reactivity.

Journal Article Glia · September 2017 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 hypothesiz ... Full text Cite

Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?

Journal Article Epigenetics · August 2017 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, partic ... Full text Link to item Cite

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism.

Journal Article J Int Med Res · April 2017 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 ... Full text Link to item Cite

Optimized solubilization of TRIzol-precipitated protein permits Western blotting analysis to maximize data available from brain tissue.

Journal Article Journal of neuroscience methods · March 2017 BackgroundTechniques 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 ... Full text Cite

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse.

Journal Article Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · January 2017 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 ... Full text Cite

Gestational Exposure to Air Pollution Alters Cortical Volume, Microglial Morphology, and Microglia-Neuron Interactions in a Sex-Specific Manner.

Journal Article Frontiers in synaptic neuroscience · January 2017 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 worl ... Full text Cite

Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on microglial function and neuroinflammation during development.

Journal Article The Journal of steroid biochemistry and molecular biology · June 2016 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 th ... Full text Cite

Unmasking silent neurotoxicity following developmental exposure to environmental toxicants.

Journal Article Neurotoxicology and teratology · May 2016 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 natur ... Full text Cite

Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection.

Journal Article Brain Behav Immun · January 2016 Featured Publication 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 ... Full text Link to item Cite

A model for the induction of autism in the ecosystem of the human body: the anatomy of a modern pandemic?

Journal Article Microb Ecol Health Dis · 2015 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 ... Full text Link to item Cite

Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta.

Journal Article Gut Microbes · 2015 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 ... Full text Link to item Cite

Examination of sex and minocycline treatment on acute morphine-induced analgesia and inflammatory gene expression along the pain pathway in Sprague-Dawley rats.

Journal Article Biology of sex differences · January 2015 BackgroundIn 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 de ... Full text Cite

Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms.

Journal Article Dialogues in clinical neuroscience · September 2014 Featured Publication 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 ... Cite

Neonatal infection modulates behavioral flexibility and hippocampal activation on a Morris Water Maze task.

Journal Article Physiology & behavior · April 2014 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 neurona ... Full text Cite

Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring.

Journal Article Brain, behavior, and immunity · March 2014 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 p ... Full text Cite

FACS analysis of neuronal-glial interactions in the nucleus accumbens following morphine administration.

Journal Article Psychopharmacology · December 2013 RationaleGlia, 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 t ... Full text Cite

Neonatal E. coli infection causes neuro-behavioral deficits associated with hypomyelination and neuronal sequestration of iron.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · October 2013 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, h ... Full text Cite

Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice.

Journal Article Environmental health perspectives · September 2013 BackgroundLow 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 healt ... Full text Cite

Chemokines and the hippocampus: a new perspective on hippocampal plasticity and vulnerability.

Journal Article Brain, behavior, and immunity · May 2013 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 endurin ... Full text Cite

Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system.

Journal Article Hormones and behavior · May 2013 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 ... Full text Cite

Adolescent morphine exposure affects long-term microglial function and later-life relapse liability in a model of addiction.

Journal Article J Neurosci · January 16, 2013 Featured Publication 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 ... Full text Link to item Cite

Microglia and Neurodevelopment: Programming of Cognition throughout the Lifespan

Chapter · January 1, 2013 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 ... Full text Cite

The outdoor air pollution and brain health workshop.

Journal Article Neurotoxicology · October 2012 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 ... Full text Cite

Sex, glia, and development: interactions in health and disease.

Journal Article Horm Behav · August 2012 Featured Publication 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 ste ... Full text Link to item Cite

The immune system and developmental programming of brain and behavior.

Journal Article Front Neuroendocrinol · August 2012 Featured Publication 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 du ... Full text Link to item Cite

Special Issue: the neuroendocrine-immune axis in health and disease.

Journal Article Hormones and behavior · August 2012 Full text Cite

Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · July 2012 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 weigh ... Full text Cite

Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus.

Journal Article Brain, behavior, and immunity · March 2012 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 t ... Full text Cite

Sex differences in microglial colonization of the developing rat brain.

Journal Article Journal of neurochemistry · March 2012 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 pr ... Full text Cite

Is autism a member of a family of diseases resulting from genetic/cultural mismatches? Implications for treatment and prevention.

Journal Article Autism Res Treat · 2012 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, ... Full text Link to item Cite

Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression.

Journal Article J Neurosci · December 7, 2011 Featured Publication 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 profound ... Full text Link to item Cite

Microglia and memory: modulation by early-life infection.

Journal Article J Neurosci · October 26, 2011 Featured Publication 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 b ... Full text Link to item Cite

Reconstitution of the human biome as the most reasonable solution for epidemics of allergic and autoimmune diseases.

Journal Article Med Hypotheses · October 2011 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 ... Full text Link to item Cite

A Lifespan Approach to Neuroinflammatory and Cognitive Disorders: A Critical Role for Glia.

Journal Article Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · August 2011 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 activatio ... Full text Cite

LPS elicits a much larger and broader inflammatory response than Escherichia coli infection within the hippocampus of neonatal rats.

Journal Article Neuroscience letters · June 2011 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 ... Full text Cite

Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.

Journal Article Neurobiology of learning and memory · July 2010 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, whi ... Full text Cite

Enduring consequences of maternal obesity for brain inflammation and behavior of offspring.

Journal Article FASEB J · June 2010 Featured Publication 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 bra ... Full text Link to item Cite

Neonatal Escherichia coli infection alters glial, cytokine, and neuronal gene expression in response to acute amphetamine in adolescent rats.

Journal Article Neuroscience letters · April 2010 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 psych ... Full text Cite

Neonatal bacterial infection alters fever to live and simulated infections in adulthood.

Journal Article Psychoneuroendocrinology · April 2010 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, includ ... Full text Cite

Enduring consequences of early-life infection on glial and neural cell genesis within cognitive regions of the brain.

Journal Article Brain, behavior, and immunity · March 2010 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 ... Full text Cite

Early life environment influences on neuroimmune interactions and behavior in adulthood

Journal Article INTEGRATIVE AND COMPARATIVE BIOLOGY · February 1, 2009 Link to item Cite

Early-life programming of later-life brain and behavior: a critical role for the immune system.

Journal Article Frontiers in behavioral neuroscience · January 2009 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., slee ... Full text Cite

Early-life infection leads to altered BDNF and IL-1beta mRNA expression in rat hippocampus following learning in adulthood.

Journal Article Brain, behavior, and immunity · May 2008 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 i ... Full text Cite

Bacterial infection early in life protects against stressor-induced depressive-like symptoms in adult rats.

Journal Article Psychoneuroendocrinology · April 2008 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 ha ... Full text Cite

Genetic resistance to infection influences a male's sexual attractiveness and modulation of testosterone.

Journal Article Brain, behavior, and immunity · March 2008 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 fro ... Full text Cite

Stressor-specific alterations in corticosterone and immune responses in mice.

Journal Article Brain, behavior, and immunity · January 2008 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 ... Full text Cite

Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood.

Journal Article Brain, behavior, and immunity · March 2007 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 (lipopolys ... Full text Cite

A behavioural characterization of neonatal infection-facilitated memory impairment in adult rats.

Journal Article Behavioural brain research · April 2006 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 lipopolys ... Full text Cite

Cardiac arrest/cardiopulmonary resuscitation augments cell-mediated immune function and transiently suppresses humoral immune function.

Journal Article Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · November 2005 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 car ... Full text Cite

Neonatal infection-induced memory impairment after lipopolysaccharide in adulthood is prevented via caspase-1 inhibition.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · August 2005 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 ma ... Full text Cite

Neonatal infection induces memory impairments following an immune challenge in adulthood.

Journal Article Behavioral neuroscience · February 2005 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 E ... Full text Cite

Short day lengths enhance skin immune responses in gonadectomised Siberian hamsters.

Journal Article Journal of neuroendocrinology · January 2005 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 s ... Full text Cite

Exogenous pyruvate prevents stress-evoked suppression of mitogen-stimulated proliferation.

Journal Article Brain, behavior, and immunity · September 2004 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 compro ... Full text Cite

Effects of photoperiod history on immune responses to intermediate day lengths in Siberian hamsters (Phodopus sungorus).

Journal Article Journal of neuroimmunology · April 2004 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 fol ... Full text Cite

Peripubertal immune challenges attenuate reproductive development in male Siberian hamsters (Phodopus sungorus).

Journal Article Biology of reproduction · March 2004 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 exp ... Full text Cite

Photoperiod influences the effects of exercise and food restriction on an antigen-specific immune response in Siberian hamsters.

Journal Article Endocrinology · February 2004 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 ... Full text Cite

Photoperiod controls the induction, retention, and retrieval of antigen-specific immunological memory.

Journal Article American journal of physiology. Regulatory, integrative and comparative physiology · January 2004 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 ... Full text Cite

Sex differences in photoperiodic and stress-induced enhancement of immune function in Siberian hamsters.

Journal Article Brain, behavior, and immunity · December 2003 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 ... Full text Cite

Photoperiod affects the expression of sex and species differences in leukocyte number and leukocyte trafficking in congeneric hamsters.

Journal Article Psychoneuroendocrinology · November 2003 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 ... Full text Cite

Photoperiod alters the time course of brain cyclooxygenase-2 expression in Siberian hamsters.

Journal Article Journal of neuroendocrinology · October 2003 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- ... Full text Cite

Blunted stress responses in delayed type hypersensitivity in mice lacking the neuronal isoform of nitric oxide synthase.

Journal Article Journal of neuroimmunology · July 2003 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-hype ... Full text Cite

Photoperiodic adjustments in immune function protect Siberian hamsters from lethal endotoxemia.

Journal Article Journal of biological rhythms · February 2003 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 ... Full text Cite

Melatonin regulates energy balance and attenuates fever in Siberian hamsters.

Journal Article Endocrinology · July 2002 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 melato ... Full text Cite

Short day lengths augment stress-induced leukocyte trafficking and stress-induced enhancement of skin immune function.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · March 2002 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 ani ... Full text Cite

Short day lengths attenuate the symptoms of infection in Siberian hamsters.

Journal Article Proceedings. Biological sciences · March 2002 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 e ... Full text Cite

Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist.

Journal Article American journal of physiology. Regulatory, integrative and comparative physiology · May 2001 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 functio ... Full text Cite

Behavioral phenotyping of transgenic and knockout animals: a cautionary tale.

Journal Article Lab animal · January 2001 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. ... Cite

Sex steroid hormones enhance immune function in male and female Siberian hamsters.

Journal Article American journal of physiology. Regulatory, integrative and comparative physiology · January 2001 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 ... Full text Cite

Anticholinergic effects in frogs in a Morris water maze analog.

Journal Article Physiology & behavior · May 2000 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 visua ... Full text Cite

Lipopolysaccharide facilitates partner preference behaviors in female prairie voles.

Journal Article Physiology & behavior · December 1999 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 ... Full text Cite