Staci D. Bilbo
  • Staci D. Bilbo

  • Associate Professor in the Department of Psychology and Neuroscience
  • Psychology and Neuroscience
  • 3016
  • Campus Box 91050
  • Phone: (919) 681-7262, (919) 681-7005
  • Fax: (919) 660-5798
  • Homepage
  • Curriculum Vitae
  • Overview

    We explore interactions between the nervous and immune systems, and how these interactions influence complex behavior such as cognition and emotion. Far beyond its role in host defense, there is mounting evidence for the vital role the immune system plays within the brain, in both normal, “homeostatic” processes (e.g., sleep, metabolism), as well as in pathology, when the dysregulation of immune molecules may occur. 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. Notably, 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 autism. Thus, the proximate goal of my research program is to determine how seemingly disparate challenges during the perinatal period of life, such as infection, stressors, or toxins, may converge on the immune system and thereby markedly influence brain development, as well as cognitive and affective behaviors throughout the remainder of the lifespan. Conversely, we are also exploring how interventions, such as nurturing maternal care or environmental enrichment, can work to counteract the deleterious effects of early-life infection, trauma, or stress, again via their impact on neuroimmune communication.
  • Other

    Richa Hanamsagar -- Postdoctoral Colleague; Michael Lacagnina -- Graduate Student; Carina Block -- Graduate Student; Christine Belliveau -- Associate in Research; Melanie Wiley -- Associate in Research; Stewart Cox -- Associate in Research; Bailey Ryan -- Undergraduate Researcher; Sammie Truong -- Undergraduate Researcher; Dominic Le -- Undergraduate Researcher Haley Sullivan -- Undergraduate Researcher
  • Specialties

    • Systems and Integrative Neuroscience
    • Cognition and Cognitive Neuroscience
  • Areas of Interest

    Cytokines and Cognition
    Developmental Programming
    Neural-Glial Interactions
  • Education

      • Ph.D.,
      • Johns Hopkins University,
      • 2003
      • MA Psychology,
      • The Johns Hopkins University,
      • 2000
      • BA Psychology,
      • The University of Texas at Austin,
      • 1998
      • B.A.,
      • University of Texas at Austin,
      • 1998
  • Awards, Honors and Distinctions

      • Bass Connections Team Leader,
      • Brain and Society Theme,
      • June, 2013 - May 2014
      • Frank Beach Young Investigator Award,
      • Society for Behavioral Neuroendocrinology,
      • November 2011
      • DIBS Research Incubator Award,
      • Duke Institute for Brain Sciences,
      • July, 2010
      • Robert Ader New Investigator Award,
      • PsychoNeuroImmunology Research Society,
      • May, 2009
      • NIMH Individual Ruth L. Kirschstein NRSA,
      • NIMH,
      • 2005-2008
      • PsychoNeuroImmunology Research Society Scholars Award,
      • 2005
      • PsychoNeuroImmunology Research Society Travel Award,
      • 2004
      • Women in Neuroscience Travel Award,
      • 2003
      • American Psychological Association Science Directorate Dissertation Research Award,
      • 2002
      • PsychoNeuroImmunology Research Society Travel Award,
      • 2002
      • Society for Behavioral Neuroendocrinology Annual Meeting Student Travel Award,
      • 2002
      • Society for Neuroscience, Melatonin Club Reception Poster Award,
      • 2002
      • Society for Behavioral Neuroendocrinology Annual Meeting Student Travel Award,
      • 2001
      • Society for Neuroscience, Melatonin Club Reception Best Poster Award,
      • 1999
      • Graduation with Honors and Special Honors in Psychology, The University of Texas,
      • 1998
      • Psi Chi Undergraduate Research Fair Best Poster Award,
      • 1998
      • Society for Behavioral Neuroendocrinology Annual Meeting Poster Award,
      • 1998
      • The University of Texas Undergraduate Research Fellowship,
      • 1997-1998
      • University of Texas Psi Chi chapter President,
      • 1997-1998
      • Psi Chi, National Honor Society in Psychology,
      • 1996-1998
      • The University of Texas at Austin Undergraduate Special Merit Scholarship,
      • 1994-1995
  • Selected Publications

      • LL Williamson, PW Sholar, RS Mistry, SH Smith and SD Bilbo.
      • 2011.
      • Microglia and memory: modulation by early-life infection..
      • J Neurosci
      • 31:
      • 15511-15521
      • .
      Publication Description

      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.

      • JM Schwarz, MR Hutchinson and SD Bilbo.
      • 2011.
      • Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression..
      • J Neurosci
      • 31:
      • 17835-17847
      • .
      Publication Description

      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.

      • JM Schwarz, PW Sholar and SD Bilbo.
      • 2012.
      • Sex differences in microglial colonization of the developing rat brain..
      • J Neurochem
      • 120:
      • 948-963
      • .
      Publication Description

      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.

      • SD Bilbo and V Tsang.
      • 2010.
      • Enduring consequences of maternal obesity for brain inflammation and behavior of offspring..
      • FASEB J
      • 24:
      • 2104-2115
      • .
      Publication Description

      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.

      • SD Bilbo and JM Schwarz.
      • 2012.
      • The immune system and developmental programming of brain and behavior..
      • Front Neuroendocrinol
      • 33:
      • 267-286
      • .
      Publication Description

      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.

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  • Postdoctoral Students

    • Richa Hanamsagar
      • June 10, 2013 - present
    • Susan Smith
      • May, 2010 - May, 2012
    • Nicole Huff
      • January 1, 2010 - February, 2012
    • Jaclyn M Schwarz
      • October 1, 2008 - December, 2012
  • Teaching

    • NEUROSCI 114
    • PSY 156