Glial progenitor cells in normal and pathological states.

We have been studying glial progenitor cells by using antibodies against the NG2 proteoglycan and the alpha receptor for platelet-derived growth factor (PDGF alpha R). In vitro the two molecules are expressed on oligodendrocyte progenitor cells but are down-regulated as they differentiate into mature oligodendrocytes. In vivo, they are found not only during development but also exist abundantly throughout the gray and white matter of the mature brain and are distinct from astrocytes or microglia. A small fraction of NG2+ cells in the early postnatal brain differentiates into oligodendrocytes in vivo. We examined changes in NG2+/PDGF alpha R+ cells in the dysmyelinating mutant jimpy, which arises as a result of a point mutation in the proteolipid protein gene and is characterized by severe dysmyelination accompanied by premature oligodendrocyte death. In the spinal cords of jimpy mice at postnatal day 18, there was a three- to six-fold increase in the number of NG2+ glial cells that had incorporated bromodeoxyuridine compared with that in the wild type spinal cord. To identify signals responsible for the increased proliferation of oligodendrocyte progenitor cells, mRNAs isolated from jimpy and wild type mice were assayed for various cytokines. There was no significant change in the levels of PDGF A or TGF-beta, but there was a significant increase in the level of the chemokine GRO alpha in the jimpy spinal cord. We are currently testing the possibility that GRO alpha directly acts on glial progenitor cells and stimulates their proliferation.