The myelin sheath is essential for normal conduction in major nerve tracks. Therefore neurological dysfunction occurs in demyelinating diseases such as multiple sclerosis (MS) and viral encephalitis. We study how myelin-forming cells can develop and regenerate both in vitro and in vivo. Molecular analysis of oligodendrocyte type 2 astrocyte (O-2A) progenitor cells reveals that FGF modulates the PDGF-driven pathway of oligodendrocyte development by up-regulating the PDGF receptor on these cells. In a chemotaxis chamber assay PDGF, but not FGF, can trigger directed migration which can occur in the absence of mitosis. O-2A lineage cells were isolated and cultured from mice with a demyelinating disease caused by a corona virus. Cultures from demyelinated tissue differed in several ways from those of the controls: (1) the total number of O-2A lineage cells was dramatically increased; (2) the O-2A cells consisted of a high proportion of 04 positive astrocytes and of cells with a mixed oligodendrocyte-astrocyte lineage; (3) all O-2A cells showed enhanced proliferation in response to an episode of demyelination. In particular a large proportion of progenitor cells were incorporating DNA. Our in vitro analysis of adult human brain cells also suggests the existence of a """"""""resting"""""""" oligodendrocyte precursor cell with an antigenic phenotype similar to that seen in rodents. Thus, our interest lies in the characterization of the oligodendrocyte precursor cells present in the adult CNS and their role in remyelination.
