Epidermal Growth Factor and Fibroblast Growth Factor-2 Have Different Effects on Neural Progenitors in the Adult Rat Brain

TLDR

Neurons and glia are generated throughout adulthood from proliferating cells in the subventricular zone and hippocampus. The study investigates the differential, site‑specific effects of exogenous FGF‑2 and EGF on progenitor cells in vivo. After two weeks of intracerebroventricular administration, both FGF‑2 and EGF expanded the SVZ progenitor pool, yet only FGF‑2 increased newborn neurons in the olfactory bulb, whereas EGF reduced neuronal output, promoted astrocyte formation, and increased non‑neuronal cells in the striatum without neuronal differentiation, while neither factor affected hippocampal progenitor proliferation, these results illuminate growth‑factor roles in adult neurogenesis and inform neuronal replacement strategies.

Abstract

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 differential and site-specific effects on progenitor cells in vivo. Both growth factors expanded the SVZ progenitor population after 2 weeks of intracerebroventricular administration, but only FGF-2 induced an increase in the number of newborn cells, most prominently neurons, in the olfactory bulb, the normal destination for neuronal progenitors migrating from the SVZ. EGF, on the other hand, reduced the total number of newborn neurons reaching the olfactory bulb and substantially enhanced the generation of astrocytes in the olfactory bulb. Moreover, EGF increased 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 were associated closely with striatal neurons. The proliferation of hippocampal progenitors was not affected by either growth factor. However, EGF increased the number of newborn glia and reduced the number of newborn neurons, similar to the effects seen in the olfactory bulb. These findings may be useful for elucidating the in vivo role of growth factors in neurogenesis in the adult CNS and may aid development of neuronal replacement strategies after brain damage.