Growth factor treatment promotes mobilization of young but not aged adult subventricular zone precursors in response to demyelination.

Precursor cells of the adult mouse subventricular zone (SVZ) are mobilized and recruited by a lysolecithin (LPC)-induced demyelination of the corpus callosum. Because age decreases the proliferation of the SVZ neural precursors as well as the potential for myelin repair of the adult central nervous system, we have compared the ability of young and aged adult neural precursors to respond to LPC-induced demyelination. With age, the SVZ cells lost their capacity to proliferate and to be recruited by the lesion. Whereas a single injection of fibroblast growth factor-2 or transforming growth factor-alpha stimulated the proliferation of SVZ and rostral migratory stream precursors in both groups of animals after demyelination, they favored recruitment at the lesion in young mice but not in aged ones. In vitro experiments using neurospheres derived from young and aged animals indicated that both populations have the same migratory performances. Our in vivo data thus suggest that aged neural precursors may loose their intrinsic capacities to respond to demyelination-induced signals. Alternatively, their function may be altered by modification of the aged extracellular environment.