Neonatal exposure to bacteria in rats leads to memory impairment following an immune challenge in adulthood. The proposed research will explore this phenomenon by examining 1) the role of the pro- inflammatory cytokine interleukin [IL]-1beta, 2) the mechanism(s) underlying cytokine-induced memory impairment, and 3) the generality of the phenomenon. To test the hypothesis that IL-1 produced in response to an immune challenge (LPS) in adulthood impairs memory, an IL-1 synthesis inhibitor will be administered prior to the learning experience and subsequent LPS, which normally impairs memory in neonatally-infected rats. To determine the mechanism(s) underlying cytokine-induced memory impairment, adult rats treated as neonates with bacteria or PBS will be injected with LPS or saline, and cytokine and glial cell marker gene expression will be measured in the hippocampus. LTP and BDNF expression will be measured in the hippocampus following LPS. To determine the generality of these effects, rats will be infected prenatally or neonatally with bacteria or virus, and behavioral consequences will be measured in adults. The duration of memory impairment will also be measured, and a number of memory paradigms will be tested.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32MH076320-01
Application #
7052678
Study Section
Special Emphasis Panel (ZRG1-F02A (20))
Program Officer
Curvey, Mary F
Project Start
2005-09-01
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
University of Colorado at Boulder
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Bilbo, Staci D (2013) Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system. Horm Behav 63:684-91
Bilbo, Staci D; Schwarz, Jaclyn M (2012) The immune system and developmental programming of brain and behavior. Front Neuroendocrinol 33:267-86
Bland, Sondra T; Beckley, Jacob T; Watkins, Linda R et al. (2010) Neonatal Escherichia coli infection alters glial, cytokine, and neuronal gene expression in response to acute amphetamine in adolescent rats. Neurosci Lett 474:52-7
Bilbo, Staci D; Yirmiya, Raz; Amat, Jose et al. (2008) Bacterial infection early in life protects against stressor-induced depressive-like symptoms in adult rats. Psychoneuroendocrinology 33:261-9
Bilbo, Staci D; Barrientos, Ruth M; Eads, Andrea S et al. (2008) Early-life infection leads to altered BDNF and IL-1beta mRNA expression in rat hippocampus following learning in adulthood. Brain Behav Immun 22:451-5
Bilbo, Staci D; Newsum, Nicholas J; Sprunger, David B et al. (2007) Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood. Brain Behav Immun 21:332-42