Evidence that perinatal and adult NG2-glia are not conventional oligodendrocyte progenitors and do not depend on axons for their survival

Abstract

In the adult CNS, cells that express the NG2 chondroitin sulphate proteoglycan are considered oligodendrocyte progenitor cells (OPCs). However, adult NG2-glia are highly complex cells, suggesting they may be a mature glial cell type distinct from conventional OPCs. To test this possibility, we have determined the response of NG2-glia to axon loss in the neonatal rat optic nerve, which has been shown previously to result in an almost complete loss of OPCs. We show here that NG2-glia are not lost following enucleation of the neonatal or juvenile optic nerve and that at all ages NG2-glia become “reactive” in response to axon degeneration, in direct contrast to previous studies on OPCs. We provide evidence that NG2-glia with an adult morphological phenotype develop postnatally, at the same time as oligodendrocytes. In the neonatal nerve, we show that the loss of axons blocks the development of oligodendrocytes, although reactive NG2-glia are abundant and are able to generate oligodendrocytes when placed in culture. Conversely, axon transection did not result in the loss of mature oligodendrocytes, indicating that the dependence of oligodendrocytes on axon-derived survival factors decreases with differentiation. This study shows that NG2-glia are a highly reactive cell type and do not generate oligodendrocytes in vivo in the absence of appropriate axon-derived signals. This may underlie in part the failure of remyelination in chronic multiple sclerosis, despite the abundance of NG2+ expressing glial cells within demyelinated lesions. It is clear either that OPCs do not depend on axons for their survival, in total contradiction to previous studies, or that in vivo a population of NG2 expressing glia are not perinatal or adult OPCs in the accepted sense. We suggest that a population of NG2-glia diverge postnatally into a novel glial type that is functionally and behaviourally distinct from conventional OPCs.