Immune Activation, Hippocampal IL-1beta, and Memory

免疫激活、海马 IL-1beta 和记忆

• 批准号: 6750725
• 负责人: JERRY Weeks RUDY
• 金额: $ 29.06万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6750725
• 关键词: Escherichia coli; auditory stimulus; brain derived neurotrophic factor; cognition disorders; conditioning; cues; cytokine receptors; disease /disorder model; enzyme linked immunosorbent assay; fear; hippocampus; immune system; interleukin 1; laboratory rat; lipopolysaccharides; long term memory; memory; memory disorders; microinjections; neural information processing; neuroimmunomodulation; polymerase chain reaction; protein structure function; serotonin; short term memory; tissue /cell culture; zymosan

The causes of many cognitive and memory disturbances are poorly understood. However, many of these disturbances (e.g., Alzheimer's disease, AIDS dementia, autoimmune disease, viral diseases such as Borna virus, normal aging, cancer and cancer chemotherapy) are associated with elevated levels of peripheral and/or brain cytokines, which are immune products released in response to infection. Some researchers have speculated that cognitive impairments are part of the "sickness pattern" produced by cytokines and that increased brain levels of a particular cytokine, IL-1beta, may play a key role in the production of these phenomena. However, the hypothesis that brain IL-1beta, or other cytokines produce cognitive/memory disturbances has received little systematic attention. The goal of this proposal is to systematically explore the implications of this hypothesis. We will do this by building on our past work to (a) determine if IL-1beta, impairs long-term memory consolidation on a range of tasks that depend on the hippocampus, (b) determine if IL-1beta, also impairs short-term memory, (c) determine if such memory impairments can be produced by naturally occurring conditions that induce IL-1beta, in the hippocampus such as infection, and (d) examine the hypothesis that IL-1beta, produces its effects on memory by its influence on brain derived neurotrophic factor (BDNF). Thus, the proposed research will contribute to an understanding of disorders of memory, the operation of IL-1beta, in the brain, and the mechanisms that underlie learning and memory.

许多认知和记忆障碍的原因知之甚少。 然而，许多这些干扰（例如，阿尔茨海默病、AIDS痴呆、自身免疫性疾病、病毒性疾病如博尔纳病毒、正常衰老、癌症和癌症化疗）与外周和/或脑细胞因子水平升高有关，所述细胞因子是响应于感染而释放的免疫产物。 一些研究人员推测，认知障碍是由细胞因子产生的“疾病模式”的一部分，并且特定细胞因子IL-1 β的大脑水平增加可能在这些现象的产生中发挥关键作用。 然而，脑IL-1 β或其他细胞因子产生认知/记忆障碍的假设很少受到系统的关注。 本提案的目的是系统地探讨这一假设的含义。我们将在我们过去的工作基础上进行这项工作，以（a）确定IL-1 β是否会损害依赖海马体的一系列任务的长期记忆巩固，（B）确定IL-1 β是否也会损害短期记忆，（c）确定这种记忆障碍是否可以由海马体中诱导IL-1 β的自然发生的条件（如感染）产生，和（d）检验IL-1 β通过影响脑源性神经营养因子（BDNF）而对记忆产生影响的假设。 因此，拟议的研究将有助于理解记忆障碍，IL-1 β在大脑中的作用，以及学习和记忆的基础机制。