The long term objectives of this proposal are to explore the biochemical properties of intermediate filaments of the nervous system, and the biology of oligodendroglia and astrocytes. The processes of assembly of neurofilament subunits, isolated from rat and bovine CNS, will be studied by turbindimetry and electron microscopy (and new techniques under development). The role of each subunit in this process and the interaction of neurofilaments with other cytoskeletal proteins will be explored by displacement reactions. Neurofilament synthesis will be studied in cell-free systems and metabolism will be studied in normal and toxin-perturbed rats. Long-term cultures of rat oligodendroglia will be characterized and the ability of differentiated oligodendrocytes to divide will be defined. Biochemical studies of oligodendroglia in culture will include protein analysis and biosynthesis, cell-specific enzymes and lipid analyses. Two monoclonal antibodies to oligodendroglia will be further characterized. Attempts to obtain pure cultures of bulk-isolated astrocytes will continue, as will collaborative studies on the glycosphingolipid composition of glial cells. These fundamental studies have implications for conditions such as Alzheimer's disease and toxic neuropathies that involve intermediate filament pathology, and for demyelinating conditions in which stimulation of the possible multiplication of mature oligodendroglia would be desirable.
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