STACI D. BILBO

HOME	CURRENT PROJECTS Developmental Origins of Risk & Resilience: The broad goal of research in this laboratory is to understand how the early life environment of an individual may influence the immune factors involved in setting a so-called trajectory of "protection or pathology" in brain and behavior. We have been working to specifically understand the role of innate CNS immune cells, in particular microglia and astrocytes, and their inflammatory products such as cytokines and chemokines, on cognitive processes in rats. Briefly, we have demonstrated that systemic infection with bacteria (Escherichia coli) on postnatal day (P) 4 in rats is associated with dramatic hippocampal-dependent memory impairments in adulthood. However, these impairments are only observed if a second immune challenge (bacterial lipopolysaccharide [LPS]) is administered around the time of learning in adulthood. Notably, the memory impairment is linked with increased brain microglial cell reactivity and exaggerated pro-inflammatory cytokine (interleukin [IL]-1β) production to the LPS, and preventing the synthesis of IL-1 prior to the LPS completely reverses the memory impairment. Importantly, E. coli infection later in development, on P30, does not result in long-term changes in glial function, or memory impairment following an immune challenge in adulthood. Thus, infection specifically during the neonatal period appears to act as a “vulnerability” factor, by altering the adult brain’s response to the subsequent immune challenge, which then influences memory (See Figure 2; Bilbo & Schwarz, Frontiers in Behavioral Neuroscience, 2009). From these data, the goal of the ongoing research is to address two related questions: 1) what changes occur in the neonatal brain in response to the infection that render the brain vulnerable versus resistant to a later challenge? and 2) what are the long-term consequences for host morbidity and mortality? Beyond this, we are extending these novel findings in response to infection to other early life events, including maternal/neonatal stressors, drugs of abuse, and dietary changes (e.g., maternal obesity). These seemingly disparate challenges all appear to activate glial cells via the innate immune system’s pattern recognition receptors, toll-like receptors (TLRs), which have been referred to as generic “danger” receptors. Taken together, we believe that the potential neuroimmune mechanisms underlying such seemingly disparate challenges have been relatively ignored, and may in fact share many similarities. If true, then these collective data should provide novel insight into the influence of early immune activation on neural and immune system development, the role that the brain’s immune response plays in cognition, and ultimately treatment decisions. READ PRESS RELEASE ABOUT THIS WORK LISTEN TO RADIO CLIP ABOUT THIS WORK (REQUIRES REAL PLAYER)
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CURRENT PROJECTS

Developmental Origins of Risk & Resilience:

The broad goal of research in this laboratory is to understand how the early life environment of an individual may influence the immune factors involved in setting a so-called trajectory of "protection or pathology" in brain and behavior. We have been working to specifically understand the role of innate CNS immune cells, in particular microglia and astrocytes, and their inflammatory products such as cytokines and chemokines, on cognitive processes in rats. Briefly, we have demonstrated that systemic infection with bacteria (Escherichia coli) on postnatal day (P) 4 in rats is associated with dramatic hippocampal-dependent memory impairments in adulthood. However, these impairments are only observed if a second immune challenge (bacterial lipopolysaccharide [LPS]) is administered around the time of learning in adulthood. Notably, the memory impairment is linked with increased brain microglial cell reactivity and exaggerated pro-inflammatory cytokine (interleukin [IL]-1β) production to the LPS, and preventing the synthesis of IL-1 prior to the LPS completely reverses the memory impairment. Importantly, E. coli infection later in development, on P30, does not result in long-term changes in glial function, or memory impairment following an immune challenge in adulthood. Thus, infection specifically during the neonatal period appears to act as a “vulnerability” factor, by altering the adult brain’s response to the subsequent immune challenge, which then influences memory (See Figure 2; Bilbo & Schwarz, Frontiers in Behavioral Neuroscience, 2009).

From these data, the goal of the ongoing research is to address two related questions: 1) what changes occur in the neonatal brain in response to the infection that render the brain vulnerable versus resistant to a later challenge? and 2) what are the long-term consequences for host morbidity and mortality? Beyond this, we are extending these novel findings in response to infection to other early life events, including maternal/neonatal stressors, drugs of abuse, and dietary changes (e.g., maternal obesity). These seemingly disparate challenges all appear to activate glial cells via the innate immune system’s pattern recognition receptors, toll-like receptors (TLRs), which have been referred to as generic “danger” receptors. Taken together, we believe that the potential neuroimmune mechanisms underlying such seemingly disparate challenges have been relatively ignored, and may in fact share many similarities. If true, then these collective data should provide novel insight into the influence of early immune activation on neural and immune system development, the role that the brain’s immune response plays in cognition, and ultimately treatment decisions.

READ PRESS RELEASE ABOUT THIS WORK

LISTEN TO RADIO CLIP ABOUT THIS WORK (REQUIRES REAL PLAYER)