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

Eur J Neurosci. 2007 Oct;26(7):1765-79. doi: 10.1111/j.1460-9568.2007.05820.x. Epub 2007 Sep 20.

Abstract

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 beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Count
  • Cell Growth Processes / drug effects*
  • Dendrites / drug effects*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Functional Laterality
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / cytology*
  • Hippocampus / drug effects
  • Injections, Intraventricular / methods
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Neurons / cytology*
  • Neurons / drug effects*
  • Neuropeptides / metabolism
  • Rats
  • Rats, Inbred F344
  • Tubulin / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Tubb3 protein, rat
  • Tubulin
  • doublecortin protein
  • Fibroblast Growth Factor 2
  • Bromodeoxyuridine