Microglia have been implicated as key players in the inflammatory responses to many degenerative brain pathologies, including AIDS dementia, trauma, abscess, focal eschemia, EAE, MS and Alzheimer's disease. The information presently available about microglia is incomplete. Our hypothesis is that microglia may arise from the differentiation of stem cells that also give rise to other myeloid cells. However, the roles played by differentiated microglia in vivo are different from macrophages and are determined in major part by the proteins that are expressed after their differentiation. One of the major obstacles to defining microglial function in vivo during pathological events is the lack of reagents that definitively distinguish microglia from macrophages. We propose to identify novel and known microglial proteins that distinguish microglia from macrophages and/or that are induced by CNS inflammation. We will compare the patterns of expression of these mRNAs in both in vitro models in which microglial function is well-defined and in vivo models of inflammation with acute, chronic and relapsing phenotypes. Cumulatively, these studies will (1) allow us to recognize ensembles of proteins that are active in different neuropathologies, (2) define microglial in terms of unique patterns of gene expression that include not only expression of novel molecules, but a cell type specific regulation of these molecules, and (3) because this definition is molecularly based, these studies will generate a set of readily portable reagents for others studying microglial function in vivo and in vitro.

R01NS039508

2000-07-01

2007-06-30