OLIGODENDROGLIA: MYELINATION AND DEMYELINATION

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In the central nervous system, oligodendroglia elaborate extensive amounts of membranes to form the multilamellar myelin sheath which enfolds segments of axons to enhance saltatory conduction of nerve impulses. In addition to being responsible for the synthesis of this membrane, oligodendroglia also maintain it during the lifetime of the animal. During the peak of myelin production, it has been calculated that this cell type may synthesize more than three times its own weight in myelin membranes each day. In diseases chracterized by demyelination, oligodendroglia may be the target cell, and its surface components may be of particular importance. We believe that by studying the proteins and glycoproteins in oligodendroglial plasma membranes, and their genetic regulation in both the normal and diseased state, we may be able to understand the mechanism of the demyelinating process at the molecular level. We have identified and are purifying two major glycoproteins in plasma membranes that are not normally present in myelin, but are present in affected myelin and membranes from a patient with metachromatic leucodystrophy. Both monoclonal and rabbit antiserum will be produced against these purified glycoproteins for use as tools to determine if the glycoproteins are surface markers for oligodendroglia and to purify larger amounts of glycoproteins for chemical analysis. Our long term goals are to study the regulation of these two glycoproteins in oligodendroglia in the normal state and during demyelination. In other studies we plan to modify our differential plating method for obtaining oligodendroglia from neonatal rat brain to obtain them from mouse brain. Once mouse oligodendroglia are obtained, they will be characterized by immunofluorescence, electron microscopy, and incorporation studies, and the results compared with those oligodendroglia obtained from rat and bovine brain. Then oligodendroglia will be prepared from the Quaking and the Jimpy mutant mouse strains (models of abnormal myelin formation or of hypomyelination) to directly compare surface antigens, morphology, and function with normal cells. Purified oligodendroglia from these mutant mice have not been studied thus far. Our long term goals are to study gene expression at the molecular level during development and in disease.