Induction of oligodendrocyte differentiation by activators of adenylate cyclase

Oligodendrocyte differentiation is accelerated by analogs of cyclic AMP (cAMP), such as N6,2-'O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) or 8-bromo cAMP, in developing rat glial cell cultures (Raible and McMorris, 1989). However, it is not known whether the immature developing oligodendrocytes have G protein-coupled adenylate cyclase capable of generating cAMP, as would be required if development of the cells is normally regulated by endogenous cAMP. In the present study, we demonstrate that the diterpene forskolin, a potent activator of adenylate cyclase, or cholera toxin, which activates adenylate cyclase through G protein modification, can induce a precocious increase in oligodendrocyte number. When both forskolin and cholera toxin are added together, oligodendrocyte differentiation is induced to a level similar to that observed in response to cAMP analogs. These results establish for the first time that modulation of the endogenous cAMP regulatory system alters the schedule of oligodendrocyte differentiation.