Pathological studies on new functions of glial cells for the development and maintenance of myelin

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The dmy rat is an autosomal recessive mutant that exhibits severe myelin destruction. The number of oligodendrocytes decreases rapidly from 7weeks of age in the dmy rat. Hypertrophic oligodendrocytes were frequently observed, and the cytoplasm was found to be intensely positive for mitochondrial markers.We found that a G-to-A transition, 177 bp downstream of exon 3 of the Mrs2 (MRS2 magnesium homeostasis factor (Saccharomyces cerevisiae)) gene.We demonstrated an abnormal iron deposition, and significant upregulation of antioxidant enzyme heme oxygenase-1 (HO-1) and iron storage protein ferritin in the dmy rat.Immunohistochemical and Western blot analyses demonstrated a considerable reduction in the expression of major CNS myelin proteins both in the white and gray matter of mv rats. However, there was no significant difference between control and mv rats in the cell number of PLP mRNA-positive oligodendrocytes either in the white or gray matter.