Open AccessNeurogenesis and aging: FGF‐2 and HB‐EGF restore neurogenesis in hippocampus and subventricular zone of aged mice
Author(s) -
Jin Kunlin,
Sun Yunjuan,
Xie Lin,
Batteur Sophie,
Mao Xiao Ou,
Smelick Chris,
Logvinova Anna,
Greenberg David A.
Publication year - 2003
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1046/j.1474-9728.2003.00046.x
Subject(s) - neurogenesis , subgranular zone , subventricular zone , doublecortin , biology , dentate gyrus , fibroblast growth factor , hippocampal formation , bromodeoxyuridine , endocrinology , hippocampus , medicine , neuroscience , microbiology and biotechnology , neural stem cell , stem cell , immunology , immunohistochemistry , genetics , receptor
Summary 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 ∼90% in SGZ and by ∼50% in SVZ of aged mice. HB‐EGF increased BrdU labelling in SGZ at 3 months by ∼60% and at 20 months by ∼450%, which increased the number of BrdU‐labelled cells in SGZ of aged mice to ∼25% of that in young adults. FGF‐2 also stimulated BrdU labelling in SGZ, by ∼25% at 3 months and by ∼250% at 20 months, increasing the number of newborn neurones in older mice to ∼20% of that in younger mice. In SVZ, HB‐EGF and FGF‐2 increased BrdU incorporation by ∼140% at 3 months and ∼170% 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.