Perinatal Infection and Memory

围产期感染和记忆

• 批准号: 7126026
• 负责人: Staci D Bilbo
• 金额: $ 4.62万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126026
• 关键词: Escherichia coli infections; animal developmental psychology; bacterial disease; bactericidal immunity; behavior test; behavioral /social science research tag; brain derived neurotrophic factor; early experience; gene expression; glia; hippocampus; inflammation; interleukin 1; laboratory rat; lipopolysaccharides; memory disorders; newborn animals; perinatal; poly IC; postdoctoral investigator; protease inhibitor; psychoneuroimmunology

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：新生期大鼠接触细菌会导致成年期免疫挑战后记忆障碍。拟议的研究将通过检查 1) 促炎细胞因子白细胞介素 [IL]-1β 的作用，2) 细胞因子诱导的记忆障碍的机制，以及 3) 该现象的普遍性来探索这一现象。为了验证成年期免疫挑战 (LPS) 产生的 IL-1 会损害记忆这一假设，我们将在学习经历和随后的 LPS 之前给予 IL-1 合成抑制剂，这通常会损害新生感染大鼠的记忆。为了确定细胞因子诱导的记忆障碍的机制，将用细菌或 PBS 治疗的成年大鼠注射 LPS 或盐水，并测量海马中细胞因子和神经胶质细胞标记基因的表达。 LPS 后将在海马中测量 LTP 和 BDNF 表达。为了确定这些影响的普遍性，大鼠将在产前或新生儿时感染细菌或病毒，并在成年大鼠中测量行为后果。还将测量记忆障碍的持续时间，并测试一些记忆范式。

项目成果

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

生命早期的细菌感染可以防止成年大鼠出现应激源引起的抑郁样症状。

• 发表时间: 2008-04
• 影响因子: 3.7
• 作者: Bilbo, Staci D;Yirmiya, Raz;Amat, Jose;Paul, Evan D;Watkins, Linda R;Maier, Steven F
• 通讯作者: Maier, Steven F

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

新生儿处理对早期感染引起的成年认知改变的不同影响。

• 发表时间: 2007-03
• 作者: Bilbo, Staci D;Newsum, Nicholas J;Sprunger, David B;Watkins, Linda R;Rudy, Jerry W;Maier, Steven F
• 通讯作者: Maier, Steven F

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

生命早期的感染导致成年学习后大鼠海马 BDNF 和 IL-1beta mRNA 表达的改变。

• 发表时间: 2008-05
• 作者: Bilbo, Staci D;Barrientos, Ruth M;Eads, Andrea S;Northcutt, Alexis;Watkins, Linda R;Rudy, Jerry W;Maier, Steven F
• 通讯作者: Maier, Steven F