Abstract
Proliferation of oligodendrocyte progenitor cells (OPCs) is important for initial myelination as well as for remyelination in demyelinating diseases. Previously, we showed that numerous OPCs and activated microglia, are present around multiple sclerosis lesions, and that they accumulate Golli proteins. Golli proteins, present in both neuronal and immune cells, might have a role in the immune processes, as well as in development of neurons and oligodendrocytes. We hypothesize that Golli proteins, generated by microglia in response to inflammation, promote proliferation of OPCs. To test this hypothesis, we induced inflammation in neonatal mouse brain slice culture with bacterial endotoxin lipopolysaccharide (LPS). Treated slices showed an increase in the number of OPCs. Several results support the notion that this effect of LPS is conveyed through activation of microglia and upregulation of Golli proteins. First, LPSโtreated brain slices have increased expression of Golli proteins observed by immunofluorescence and Western blot analysis. Second, Golli proteins were demonstrated only in the conditioned medium from LPSโtreated microglial cell cultures (LPSโMCM), and were absent in either the conditioned media from LPSโtreated astrocytes or the control media. Third, proliferation of purified OPCs was promoted with LPSโMCM or Golli proteins, but not with LPS alone. Taken together, these results demonstrate that microglia and/or microglia secreted factors, are necessary for the LPSโpromoted proliferation of OPCs and suggest possible involvement of Golli proteins as one of mediators in this process. ยฉ 2004 WileyโLiss, Inc.