Perinatal Infection and Memory

围产期感染和记忆

• 批准号: 7052678
• 负责人: Staci D Bilbo
• 金额: $ 4.83万
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052678
• 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）：在成年后的免疫挑战后，大鼠的新生儿暴露于大鼠的细菌会导致记忆力障碍。拟议的研究将通过检查1）炎性细胞因子白介素[IL] -1BETA，2）细胞因子诱导的记忆障碍的机制以及3）现象的一般性。为了检验以响应免疫挑战（LP）（LPS）为损害记忆的假设，将在学习经验和随后的LPS之前对IL-1合成抑制剂进行施用，这通常会损害新生儿感染的大鼠的记忆。为了确定细胞因子诱导的记忆障碍的机制，将用细菌或PBS处理为新生儿的成年大鼠将注入LPS或盐水，并在海马中测量细胞因子和神经胶质细胞标记基因表达。 LTP和BDNF表达将在LPS之后的海马中测量。为了确定这些作用的一般性，将用细菌或病毒在产前或新生儿中感染大鼠，并将在成年人中测量行为后果。还将测量内存障碍的持续时间，并将测试许多内存范例。