Atypical glial cells in demyelinated and hypomyelinated mouse brains

Bis-cyclohexanone oxalyldihydrazone (cuprizone) was administered to young adult mice in order to investigate the hypothesis that the differentiation of oligodendrocyte progenitors or precursors, or of immature oligodendrocytes, might be interrupted during cuprizone intoxication. Vibratome sections were prepared from brains from control mice, mice that were fed cuprizone for 27 days and mice that were fed cuprizone for 25 days, followed by normal. diet for 2 days, and the sections were immunostained with monoclonal antibodies: MAbO4, which is directed against galactocerebroside sulfate (sulfatide); and RMAb, which is directed against galactocerebroside (GC); Process-bearing RMAb +/O4 - cells were abundant in the brains of mice that had consumed cuprizone for 27 days, and the numbers of O4-positive cells were subnormal. Two days after refeeding the normal diet the RMAb +/O4 - structures were less abundant and O4-positive cells more numerous. Moreover, the numbers of O4-positive cells were only similar to 20% of normal in the brains of hypomyelinating jimpy mutant mice, while the numbers of RMAb-positive cells were similar to 80% of normal, and the processes of the latter were associated with axons. It is suggested that RMAb +/O4 - cells in the affected brains may be process-bearing oligodendrocyte precursors containing unsulfated GC or a toxic galactolipid. (C) 1999 Elsevier Science B.V. All rights reserved.