MICROGLIAL MOLECULES INDUCED BY LENTIVIRUS INFLAMMATION

小胶质细胞被认为是中枢神经系统炎症的关键参与者 对艾滋病毒感染的反应。炎症导致星形胶质细胞增生症和神经元 丧失，与进行性艾滋病痴呆症相关的病理。类似 在其他几种退行性疾病中观察到涉及小胶质细胞的病理改变。 脑部疾病：创伤、脓肿、局灶性脑缺血、EAE、沃勒病 变性、唐氏综合症和阿尔茨海默病。这些信息 目前可获得的关于小胶质细胞处于静止状态的各种 激活的表单不完整。我们会 1.利用最新发展的分子技术--定向标签聚合酶链式反应 消减杂交和聚合酶链式反应差异显示技术鉴定 目前未知的mRNAs的cDNAs克隆 激活的小胶质细胞群。在建议的过程中 项目中，几乎所有这样的分子都将被计算在内。 2.使用这些新发现的mRNA确定在多大程度上 驻留在大脑中的小胶质细胞与大脑中的其他细胞有关 单核/巨噬细胞谱系。 3.阐明表达被激活的各种基因集合 在特定的小胶质细胞亚群中通过不同的生理和病理机制 病毒感染、慢病毒糖蛋白暴露和 细胞因子信号转导。这些数据将提示特定的mRNAs 蛋白质产品值得进行功能鉴定，因为它们 在导致艾滋病的病理生理学中可能起的作用 痴呆症。

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.