Remyelination in vitro following protein kinase C activator-induced demyelination

In previous work we found that mezerein, a C kinase activator, as well as b asic fibroblast growth factor (FGF-2) induce demyelination and partial olig odendrocyte dedifferentiation in highly differentiated aggregating brain ce ll cultures. Here we show that following protein kinase C activator-induced demyelination, effective remyelination occurs. We found that mezerein or F GF-2 caused a transient increase in DNA synthesis following a pronounced de crease of the myelin markers myelin basic protein and 2',3'-cyclic nucleoti de 3'-phosphohydrolase. Both oligodendrocytes and astrocytes were involved in this mitogenic response. Within 17 days after demyelination, myelin was restored to the level of the untreated controls. Transient mitotic activity was indispensable for remyelination. The present results suggest that myel inating oligodendrocytes retain the capacity to reenter the cell cycle, and that this plasticity is important for the regeneration of the oligodendroc yte lineage and remyelination. Although it cannot be excluded that a quiesc ent population of oligodendrocyte precursor cells was present in the aggreg ates and able to proliferate, differentiate and remyelinate, we could not f ind evidence supporting this view.