title: Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice.
abstract: 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 approximately 90% in SGZ and by approximately 50% in SVZ of aged mice. HB-EGF increased BrdU labelling in SGZ at 3 months by approximately 60% and at 20 months by approximately 450%, which increased the number of BrdU-labelled cells in SGZ of aged mice to approximately 25% of that in young adults. FGF-2 also stimulated BrdU labelling in SGZ, by approximately 25% at 3 months and by approximately 250% at 20 months, increasing the number of newborn neurones in older mice to approximately 20% of that in younger mice. In SVZ, HB-EGF and FGF-2 increased BrdU incorporation by approximately 140% at 3 months and approximately 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.
authors.affiliation: Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Sophie
authors.initials: S
authors.lastname: Batteur
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Mao
authors.forename: Chris
authors.initials: C
authors.lastname: Smelick
authors.forename: Anna
authors.initials: A
authors.lastname: Logvinova
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000375:Aging; D000818:Animals; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D006493:Heparin