MICROGLIAL MOLECULES INDUCED BY LENTIVIRUS INFLAMMATION

慢病毒炎症诱导的微胶质分子

• 批准号: 6219127
• 负责人: J GREGOR SUTCLIFFE
• 金额: $ 0.44万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219127
• 关键词: AIDS dementia complex; HIV envelope protein gp120; HIV infections; antigen presentation; complementary DNA; cytokine; cytotoxicity; disease /disorder model; flow cytometry; gene expression; genetic library; genetically modified animals; inflammation; laboratory mouse; leukocyte activation /transformation; macrophage; messenger RNA; microglia; molecular cloning; molecular pathology; neural degeneration; neuroimmunomodulation; polymerase chain reaction; subtraction hybridization; tissue /cell culture

Microglia have been implicated as key players in the CNS inflammatory response to HIV infection. Inflammation leads ti astrogliosis and neuronal loss, pathologies that correlate with progressive AIDS dementia. Similar pathologies involving microglia are observed in several other degenerative brain conditions: trauma, abscess, focal ischemia, EAE, Wallerian degeneration, Down's syndrome and Alzheimer's disease. The information presently available about microglia in their quiescent and various activated forms is incomplete. We will 1. Utilize the newly developed molecular techniques of directional tag PCR subtractive hybridization and PCR-based differential display to identify cDNA clones of presently unknown mRNAs that are selectively expressed by populations of activated microglia. During the course of the proposed project, nearly all such molecules will be accounted. 2. Determine, using these newly identified mRNAs, the degree to which brain-resident microglia are related to other cells of the monocyte/macrophage lineage. 3. Elucidate the various ensembles of genes whose expression are activated in specific microglial subsets by different physiological and pathological processes such as viral infection, lentivirus glycoprotein exposure, and cytokine signalling. These data will suggest particular mRNAs whose protein products deserve functional characterization because of their potential roles in contributing to the pathophysiology that results in AIDS dementia.

小胶质细胞在中枢神经系统炎症反应中起着关键作用。 对艾滋病毒感染的反应。 炎症导致星形胶质细胞增生和神经元 丧失，与进行性艾滋病痴呆相关的病理。 类似 在其他几种退行性疾病中也观察到涉及小胶质细胞的病理 脑部疾病：创伤、脓肿、局灶性缺血、EAE、Wallerian 退化，唐氏综合症和阿尔茨海默病。 的信息 目前可获得的关于小胶质细胞在他们的静止和各种 激活的形式是不完整的。 我们将 1. 利用新发展的定向标签PCR分子技术 差减杂交和基于PCR的差异显示来鉴定 目前未知的mRNA的cDNA克隆，其选择性地由 激活的小胶质细胞群。 在拟议的 项目，几乎所有这些分子都将被计算在内。 2. 使用这些新鉴定的mRNA， 脑内的小胶质细胞与脑内的其他细胞有关。 单核细胞/巨噬细胞谱系。 3. 阐明其表达被激活的基因的各种集合 在特定的小胶质细胞亚群中， 过程如病毒感染、慢病毒糖蛋白暴露，以及 细胞因子信号传导。 这些数据将提示特定的mRNA， 蛋白质产品值得进行功能表征，因为它们 在导致艾滋病的病理生理学中的潜在作用 痴呆