Cytokines and Memory Consolidation

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 研究IL-1β？S 1)作用部位，2)作用来源，3)机制 调节海马区依赖的背景恐惧损伤的动作。至 确定IL-1β是否作用于背侧海马区以产生 将在接受A(A)治疗的大鼠身上测试记忆障碍、情景恐惧 内源性背侧注射内毒素(外周)或(B)IL-1β(中央)注射 IL-I受体拮抗剂对海马IL-1β的抑制作用 (IL-1ra)。确定脑源性IL-Lβ的来源是否为 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 在外周注射脂多糖后。探讨IL-Lβ是否具有损伤作用 在体内通过改变背侧海马区谷氨酸释放而引起的背景恐惧 将进行微透析研究，以测量(A)未刺激和(B) 外周注射脂多糖后，KCL刺激谷氨酸释放。如果 脂多糖诱导谷氨酸释放改变，IL-1ra将注入脑内 采样区域，以确定这种改变是否被特定地调解 通过IL-1β。这些研究将回答一些重要的问题： 以及促炎细胞因子如何作用于削弱海马区依赖 记忆过程。

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.