Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice

Neurogenesis, which may contribute to the ability of the adult brain to function normally and adapt to disease, nevertheless declines with advancing age. Adult neurogenesis can be enhanced by administration of growth factors, but whether the aged brain remains responsive to these factors is unknown. We compared the effects of intracerebroventricular fibroblast growth factor (FGF)-2 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) on neurogenesis in the hippocampal dentate subgranular zone (SGZ) and the subventricular zone (SVZ) of young adult (3-month) and aged (20-month) mice. Neurogenesis, measured by labelling with bromodeoxyuridine (BrdU) and by expression of doublecortin, was reduced by similar to90% in SGZ and by similar to50% in SVZ of aged mice. HB-EGF increased BrdU labelling in SGZ at 3 months by similar to60% and at 20 months by similar to450%, which increased the number of BrdU-labelled cells in SGZ of aged mice to similar to25% of that in young adults. FGF-2 also stimulated BrdU labelling in SGZ, by similar to25% at 3 months and by similar to250% at 20 months, increasing the number of newborn neurones in older mice to similar to20% of that in younger mice. In SVZ, HB-EGF and FGF-2 increased BrdU incorporation by similar to140% at 3 months and similar to170% at 20 months, so the number of BrdU-labelled cells was comparable in untreated 3-month-old and growth factor-treated 20-month-old mice. These results demonstrate that the aged brain retains the capacity to respond to exogenous growth factors with increased neurogenesis, which may have implications for the therapeutic potential of neurogenesis enhancement in age-associated neurological disorders.