Enhanced production and dendritic growth of new dentate granule cells in the middle-aged hippocampus following intracerebroventricular FGF-2 infusions

Declined production and diminished dendritic growth of new dentate granule cells in the middle‐aged and aged hippocampus are correlated with diminished concentration of fibroblast growth factor‐2 (FGF‐2). This study examined whether increased FGF‐2 concentration in the milieu boosts both production and dendritic growth of new dentate granule cells in the middle‐aged hippocampus. The FGF‐2 or vehicle was infused into the posterior lateral ventricle of middle‐aged Fischer (F)344 rats for 2 weeks using osmotic minipumps. New cells born during the first 12 days of infusions were labeled via daily intraperitoneal injections of 5′‐bromodeoxyuridine (BrdU) and analysed at 10 days after the last BrdU injection. Measurement of BrdU+ cells revealed a considerably enhanced number of new cells in the subgranular zone (SGZ) and granule cell layer (GCL) of the dentate gyrus (DG) ipsilateral to FGF‐2 infusions. Characterization of β‐III tubulin+ neurons among newly born cells suggested an increased addition of new neurons to the SGZ/GCL ipsilateral to FGF‐2 infusions. Quantification of DG neurogenesis at 8 days post‐infusions via doublecortin (DCX) immunostaining also revealed the presence of an enhanced DG neurogenesis ipsilateral to FGF‐2 infusions. Furthermore, DCX+ neurons in FGF‐2‐infused rats exhibited enhanced dendritic growth compared with their counterparts in vehicle‐infused rats. Thus, subchronic infusion of FGF‐2 is efficacious for stimulating an enhanced DG neurogenesis from neural stem/progenitor cells in the middle‐aged hippocampus. As dentate neurogenesis is important for hippocampal‐dependent learning and memory and DG long‐term potentiation, strategies that maintain increased FGF‐2 concentration during ageing may be beneficial for thwarting some of the age‐related cognitive impairments.