THE MICROGLIAL REACTION IN SPINAL-CORDS OF JIMPY MICE IS RELATED TO APOPTOTIC OLIGODENDROCYTES

Jimpy is a shortened life-span murine mutant whose genetic disorder re sults in a severe hypomyelination in the central nervous system associ ated with a variety of glial abnormalities, including oligodendrocyte death. In this study, we report that oligodendrocyte death in jimpy oc curs through an apoptotic mechanism, as demonstrated by in situ labeli ng of nuclear DNA fragmentation. Compared to those of normal littermat es, the spinal cords of jimpy mice showed a significantly higher numbe r of apoptotic cells. Our observations also corroborate that specific glial cell death in jimpy is restricted to oligodendrocytes, as eviden ced by double labeling for DNA fragmentation and MBP immunocytochemist ry. Cells labeled for DNA fragmentation were always negative for astro glial or microglial markers. Apoptotic oligodendrocytes were not aggre gated into clusters and were ubiquitously distributed throughout the j impy spinal cord, although were more numerous in white matter than in gray matter. We found no physical association between astrocytes and d ying cells in jimpy. Microglial cells, however, were found closely att ached to and even surrounding apoptotic cells. The possible role of mi croglial cells in relation to apoptotsis is discussed.