Protein Kinase C Stimulation Induces Astrocyte and Oligodendrocyte Proliferation, Demyelination and Enhanced Remyelination in Aggregating Rat Brain Cell Cultures

The protein kinase C-activating tumor-promoter, mezerein induces cell proliferation in differentiated aggregating rat brain cell cultures. This effect was accompanied by a drastic loss of myelin constituents - like myelin basic protein and 2′,3′-cyclic nucleotide 3-phosphohydrolase - indicating that mature oligodendrocytes entering cell division dedifferentiate and lose their myelin sheath. This phase of proliferation was followed by remyelination which eventually led to higher concentrations of myelin constituents than in cultures which were not treated with mezerein. While mezerein had no effect on choline acetyltransferase, a specific neuronal marker, it induced a two-fold increase of glutamine synthetase, an astrocytic marker. These results confirm that mature oligodendrocytes and astrocytes are able to proliferate. Protein kinase-C plays a central role in stimulating oligodendrocytes as well as astrocytes. This effect on astrocytes could impair affect the process of remyelination.