Brain NGF and EGF administration improves passive avoidance response and stimulates brain precursor cells in aged male mice

Nerve growth factor (NGF) has been shown to improve damage in spatial cognition following aging, whereas epidermal growth factor (EGF) is important in brain cell proliferation. It is also known that the adult mammalian central nervous system contains persistent progenitor cells with characteristics of stem cells. These studies suggest that under appropriate external stimuli progenitor cells may generate neuronal and glial cells promoting recovery of the injured nervous system. However, little is known about the presence and responsiveness of progenitor cells in the aged brain. In the present investigation, we studied the effect of brain intracerebroventricular injections of EGF and/or NGF on progenitor cells of the subventricular area (SVZ) in aged male mice to test learning performances in the passive avoidance apparatus. We found that neither NGF nor EGF improved learning responses. However, combined NGF and EGF administration in the brain improved learning responses of aged mice in the passive avoidance when compared with aged matched nontreated controls. These findings resulted to be associated with increased immunopositivity to progenitor cells in the SVZ. The possible functional implications of these data are discussed. (C) 2002 Elsevier Science Inc. All rights reserved.