Differing in vitro survival dependency of mouse and rat NG2+ oligodendroglial progenitor cells

NG2 chondroitin sulfate proteoglycan is a surface marker of oligodendroglial progenitor cells (OPCs) in various species. In contrast to well-studied rat OPCs, however, we found that purified mouse NG2 surface positive cells (NG2(+) cells) require additional activation of cyclic AMP (cAMP) signaling for survival in a medium containing 30% B104 neuroblastoma conditioned medium supplemented with fibroblast growth factor-2 (B104CM+FGF2), whereas B104CM+FGF2 alone is sufficient for survival and selective proliferation of rat OPCs. After induction of in vitro differentiation, more than 90% of mouse NG2(+) cells became O4-positive, and a majority expressed myelin basic protein by 5 day of differentiation, which confirmed the identity of isolated mouse NG2(+) cells as OPCs. In comparison to rat OPCs, mouse OPCs in B104CM+FGF2 were less motile, and demonstrated lower basal phosphorylation levels of ERK1/2 and cAMP response element-binding protein (CREB) and a higher incidence of apoptosis mediated by the intrinsic pathway. Transient up-regulation of cAMP-CREB signaling partially inhibited apoptosis of mouse OPCs independently of the ERK pathway. This study demonstrates a difference in trophic requirements between mouse and rat OPCs, with an essential role for cAMP signaling to preserve viability of mouse OPCs.