Neuroinflammation, Inflammatory Challenge, and Memory

神经炎症、炎症挑战和记忆

基本信息

批准号：
7904790
负责人：
STEVEN F MAIER
金额：
$ 35.79万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7904790
关键词：
Age Aging Alzheimer&apos s Disease Animals Anus Astrocytes Attention Bacterial Infections Blood Brain Brain-Derived Neurotrophic Factor Cells Clinical Cognition Cognitive Coin Communication Complex Data Dendritic Cells Disease Elderly Escherichia coli Escherichia coli Infections Event Genetic Transcription Goals Hippocampus (Brain)Human IL6 gene Immune Immune system Impaired cognition Impairment Individual Infection Inflammatory Inflammatory Response Injury Interleukin-1 beta Lead Learning Life Literature Mediating Mediator of activation protein Memory Memory impairment Methods Microglia Motor Nerve Degeneration Neuroglia Norway Operative Surgical Procedures Organ Peripheral Play Postoperative Period Principal Investigator Process Production Psychological Stress Rat Strains Rattus Reporting Research Rest Risk Rodent Model Role Route Short-Term Memory Signal Transduction Stress Tumor Necrosis Factor-alpha age effect age related aged cognitive function conditioned fear cytokine design dietary restriction functional outcomes juvenile animal long term memory macrophage neuroinflammation neurotrophic factor normal aging novel prevent response senescence social stress

项目摘要

DESCRIPTION (provided by applicant): This proposal is directed at understanding some of the factors that contribute to cognitive decline during aging. It is motivated by the novel hypothesis that aging is a vulnerability factor that sensitizes or primes glial cells, thereby resulting in an age-related exaggerated brain proinflammatory cytokine (PIC) response to certain challenges. It is this sensitized PIC response, and its "downstream" products that are hypothesized to be at the core of the aged humans' (& animals') vulnerability to cognitive dysfunctions often associated with bacterial infection, surgery, and stress. The hypothesis rests on the following findings: 1) In response to infection or injury, immune cells in the periphery release PICs such as interleukin-1beta. 2) PICs can signal the brain and induce the synthesis and release of PICs in the brain, primarily by glial cells. 3) PICs in the brain, particularly ILI beta in the hippocampus, can interfere with memory consolidation, and perhaps other cognitive processes Thus, if aging sensitizes glial cells, then there should be exaggerated brain PIC responses to challenge in the aged, and a resultant impairment in memory formation. The first Aim asks whether the aged rat is more vulnerable to memory impairments associated with immune system activation and other events that induce hippocampal PICs (peripheral infection, surgery, and social stress). The second Aim asks whether glial activation, brain PICs, and downstream products of PICs, particularly reductions in brain derived neurotrophic factor (BDNF) are responsible for the age-related memory impairments produced by these challenges. The third Aim investigates whether a manipulation that is known prevent age-related glial priming, namely dietary restriction (DR), will prevent age-related exaggeration of brain PIC responses and challenge-induced memory impairments.

描述（由申请人提供）：该提案旨在理解在衰老期间导致认知能力下降的某些因素。这是由新的假设激发的，即衰老是敏感或素质细胞的脆弱因素，从而导致与年龄相关的夸张脑促炎细胞因子（PIC）对某些挑战的反应。正是这种敏感的PIC响应，其“下游”产物被认为是老年人（＆动物'）对认知功能障碍的脆弱性，通常与细菌感染，手术和压力有关。该假设取决于以下发现：1）响应感染或损伤，外围释放图片（例如白介素-1beta）中的免疫细胞。 2）图片可以发出大脑的信号，并诱导大脑中图片的合成和释放，主要是通过神经胶质细胞。 3）大脑中的图片，特别是海马中的ILIβ，可能会干扰记忆巩固，也许会干扰其他认知过程，因此，如果衰老使神经胶质细胞敏感，则应夸大大脑对老年人的挑战的反应，以及在记忆形成中产生的损害。第一个目的询问老鼠是否更容易受到与免疫系统激活相关的记忆障碍和诱发海马图片（外围感染，手术和社会压力）的其他事件。第二个目的询问图片的神经胶质激活，脑部图片和下游产品，尤其是脑衍生的神经营养因子（BDNF）的减少，负责这些挑战带来的与年龄相关的记忆障碍。第三个目标调查了已知的操纵是否可以预防与年龄相关的神经胶质启动，即饮食限制（DR），将防止与年龄相关的脑部PIC反应的夸张和挑战引起的记忆障碍。