EPIDERMAL GROWTH-FACTOR AND FIBROBLAST GROWTH-FACTOR-II HAVE DIFFERENT EFFECTS ON NEURAL PROGENITORS IN THE ADULT-RAT BRAIN

Neurons and glia are generated throughout adulthood from proliferating cells in two regions of the rat brain, the subventricular zone (SVZ) and the hippocampus. This study shows that exogenous basic fibroblast growth. factor (FGF-2) and epidermal growth factor (EGF) have differen tial and site-specific effects on progenitor cells in viva. Both growt h factors expanded the SVZ progenitor population after 2 weeks of intr acerebroventricular administration, but only FGF-2 induced an increase in the number of newborn cells, most prominently neurons, in the olfa ctory bulb, the normal destination for neuronal progenitors migrating from the SVZ. EGF, on the other hand, reduced the total number of newb orn neurons reaching the olfactory bulb and substantially enhanced the generation of astrocytes in the olfactory bulb. Moreover, EGF increas ed the number of newborn cells in the striatum either by migration of SVZ cells or by stimulation of local progenitor cells. No evidence of neuronal differentiation of newborn striatal cells was found by three- dimensional confocal analysis, although many of these newborn cells we re associated closely with striatal neurons. The proliferation of hipp ocampal progenitors was not affected by either growth factor. However, EGF increased the number of newborn glia and reduced the number of ne wborn neurons, similar to the effects seen in the olfactory bulb. Thes e findings may be useful for elucidating the in vivo role of growth fa ctors in neurogenesis in the adult CNS and may aid development of neur onal replacement strategies after brain damage.