Oligodendrocyte differentiation and progenitor cell proliferation are independently regulated by cyclic AMP

Oligodendrocytes, the glial cells specialized to synthesize myelin in the central nervous system, differentiate in primary rat brain cell cultures on a schedule similar to that observed in vivo. The schedule of oligodendrocyte differentiation and the rate of oligodendroglial progenitor cell proliferation in vitro are both modulated by 3',5'-cyclic AMP (cAMP). A 24-hour exposure to 1 mM N6,2'O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) induced a wave of oligodendrocyte differentiation but inhibited proliferation of oligodendroglial progenitors, and reduced by 30-fold the proliferation of progenitors in response to platelet-derived growth factor (PDGF). When cells were grown in the presence of maximally stimulating concentrations of PDGF, the inhibitory effect of cAMP on progenitor cell proliferation was abolished while the stimulatory effect of cAMP on oligodendrocyte differentiation remained, demonstrating that these two cAMP-regulated events are independent.