Oligodendroglial pathology in the development of myelin breakdown in the dmy mutant rat.

The dmy rat is an autosomal recessive mutant that exhibits severe myelin destruction throughout the white matter of the central nervous system. Recently, a point mutation in intron 3 of the Mrs2 has been found in the dmy rat. Mrs2 encodes an essential component of the major electrophoretic Mg(2+) influx system in mitochondria of yeast as well as human cells. In this study, we examined the morphological and numerical changes of oligodendroctyes in the development of myelin destruction in the spinal cord of the dmy rat. The number of oligodendrocytes decreases rapidly from 7weeks of age in the dmy rat in accordance with myelin breakdown. Hypertrophic oligodendrocytes were frequently observed, and the cytoplasm was found to be intensely positive for prohibitin and cytochrome oxidase, mitochondrial markers. These data suggest that mitochondrial dysfunction causes a work/compensatory hypertrophy of oligodendrocytes, resulting in direct cell death and leading to myelin destruction.