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.
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