To design
therapies for
demyelinating diseases such as
multiple sclerosis, it will be important to understand the mechanisms that control oligodendrocyte progenitor cell (OPC) numbers in the adult central nervous system (CNS). During development, OPC numbers are limited by the supply of
platelet-derived growth factor-A (
PDGF-A). Here, we examine the role of
PDGF-A in regulating OPC numbers in normal and demyelinated adult CNS using transgenic mice that overexpress
PDGF-A in astrocytes under the control of the
glial fibrillary acidic protein (GFAP) gene promoter (GFAP-
PDGF-A mice). In adult GFAP-
PDGF-A mice, there was a marked increase in OPC density, particularly in white matter tracts, indicating that the
PDGF-A supply controls OPC numbers in the adult CNS as well as during development. To discover whether increasing PDGF expression increases the number of OPCs following
demyelination and whether this enhances the efficiency of remyelination, we induced
demyelination in GFAP-
PDGF-A transgenic mice by
intraspinal injection of
lysolecithin or dietary administration of
cuprizone. In both demyelinating models, OPC density within lesions was significantly increased compared to wild-type mice. However, morphological analysis of
lysolecithin lesions did not reveal any difference in the time course or extent of remyelination between GFAP-
PDGF-A and wild-type mice. We conclude that the availability of OPCs is not rate limiting for remyelination of focal demyelinated lesions in the mouse. Nevertheless, our experiments show that it is possible to increase OPC population density in demyelinated areas by artificially increasing the supply of PDGF.