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

Authors

  • Kiranmai S. Rai,

    1. Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, NC 27710, USA
    2. Medical Research and Surgery Services, Veterans Affairs Medical Center, Durham, NC 27705, USA
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  • Bharathi Hattiangady,

    1. Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, NC 27710, USA
    2. Medical Research and Surgery Services, Veterans Affairs Medical Center, Durham, NC 27705, USA
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  • Ashok K. Shetty

    1. Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, NC 27710, USA
    2. Medical Research and Surgery Services, Veterans Affairs Medical Center, Durham, NC 27705, USA
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Dr A.K. Shetty, 1Department of surgery (Neurosurgery), as above.
E-mail: Ashok.Shetty@Duke.Edu

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 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.

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