An Apoptotic Depletion of Oligodendrocytes in the Twitcher, a Murine Model of Globoid Cell Leukodystrophy

Morphological alterations of oligodendrocytes (OLs) leading to their depletion were studied in the genetic demyelinating mutant, twitcher, a murine model of globoid cell leukodystrophy (GLD). With pi-glutathione-S-transferase immunostaining, OLs with multiple varicose processes were recognized in the early stages and adjacent areas of demyelination and then the OLs cytoplasm as well as the processes became shrunken with progression of the disease. These shrunken OLs were labeled by the TUNEL method, indicative of apoptotic cell death. The ultrastructural features of apoptotic cells were noted in these OLs and DNA laddering was noted in the twitcher brain in advanced stages. This is the first report describing the gradual depletion of OLs by apoptosis in genetic demyelination.