The long-term objectives of Project 3 are to determine, by in vivo and in vitro studies, the mechanisms by which HIV-1 mediates the functional and structural CNS pathology associated with pediatric AIDS. In addition, it is anticipated that these studies will provide new information on the contribution of microglia to the developing CNS. In vivo studies will employ immunocytochemical and histochemical methods specific for microglia and astrocytes to determine if HIV-1 interferes with normal gliogenesis. This will be done by comparing glial development in brains of fetuses from normal and from HIV-seropositive women. For the in vitro studies, selected and mixed populations of glial cells will be established to define the physiological parameters of cytokine production in culture Cytokine production will be determined by molecular biological and immunochemical methods. The contribution of specific populations of glial cells to cytokine production will be determined by in situ hybridization.
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