Cytokines and Memory Consolidation

细胞因子和记忆巩固

• 批准号: 6671457
• 负责人: RUTH M BARRIENTOS
• 金额: $ 4.64万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-27 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6671457
• 关键词: behavioral /social science research tag; fear; glutamates; hippocampus; immunocytochemistry; interleukin 1; laboratory rat; memory; microdialysis; neurotransmitter transport; postdoctoral investigator

DESCRIPTION (provided by applicant): The proposed research will explore interactions between the immune system and learning/memory processes by examining IL-1 beta?s 1) site of action, 2) source of action, and 3) mechanisms of action that mediate hippocampal dependent contextual fear impairments. To determine whether IL-1beta is acting at the dorsal hippocampus to produce memory impairments, contextual fear will be tested in rats which receive an (a) LPS (peripheral) or (b) IL-1 beta (central) injection while endogenous dorsal hippocampal IL-1 beta is being inhibited with IL-I receptor antagonist (IL-1ra). To determine whether the source of brain-derived IL-l beta is neuronal and/or glial, (a) single- and (b) double-label immunohistochemical studies will be conducted to detect cell type and cell content in hippocampus following a peripheral injection of LPS. To explore whether IL- l beta impairs contextual fear by altering dorsal hippocampal glutamate release, in vivo microdialysis studies will be conducted to measure (a) unstimulated and (b) KCl-stimulated glutamate release following a peripheral injection of LPS. If LPS induces alterations in glutamate release, IL-1ra will be infused into the sampling region to determine whether such alterations are mediated specifically by IL-1 beta. These studies will answer some important questions about where and how pro-inflammatory cytokines may act to impair hippocampal-dependent memory processes.

描述（由申请人提供）：拟议的研究将探索 免疫系统与学习/记忆过程之间的相互作用 检查 IL-1 beta 1) 作用位点，2) 作用来源，以及 3) 机制 介导海马依赖性情境恐惧障碍的作用。到 确定 IL-1beta 是否作用于背侧海马以产生 将在接受（a）的大鼠中测试记忆障碍、情境恐惧 LPS（外周）或（b）IL-1β（中枢）注射，同时内源性背侧 IL-1受体拮抗剂抑制海马IL-1β (IL-1ra)。确定脑源性IL-1β的来源是否是 神经元和/或神经胶质细胞，(a) 单标记和 (b) 双标记免疫组织化学 将进行研究以检测海马体中的细胞类型和细胞含量 外周注射 LPS 后。探讨 IL-l beta 是否会损害 通过改变体内背侧海马谷氨酸释放来产生情境恐惧 将进行微透析研究来测量（a）未刺激和（b） 外周注射 LPS 后 KCl 刺激谷氨酸释放。如果 LPS 诱导谷氨酸释放的改变，IL-1ra 将被注入 采样区域以确定此类改变是否是专门介导的 通过 IL-1 β。这些研究将回答一些重要问题： 以及促炎细胞因子如何损害海马依赖性 记忆过程。