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Neurogenesis and aging: FGF‐2 and HB‐EGF restore neurogenesis in hippocampus and subventricular zone of aged mice
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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.
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“Intracerebroventricular (ICV) injection of FGF2 induced neurogenesis in both the SVZ and SGZ (Jin et al. 2003; Mudo et al. 2009; Rai et al. 2007).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Jin et al. 2003
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Metadata
- Authors
- Jin, K., Sun, Y., Xie, L., Batteur, S., Mao, X. O., Smelick, C., Logvinova, A., & Greenberg, D. A.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Greenberg, David A.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2003-05-28
- Volume
- 2
- Issue
- 3
- Pages
- 175-183
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2091535724
- Cited by
- 396
- References
- 36
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 14 · 2020: 13 · 2019: 15 · 2018: 8 · 2017: 19 · 2016: 20 · 2015: 19 · 2014: 19 · 2013: 38 · 2012: 22
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS44110)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- adult neurogenesis, aging, FGF2, HB-EGF, dentate gyrus, subventricular zone, growth factor responsiveness, brain aging
- MeSH terms
- Aging, Animals, Cerebral Ventricles, Epidermal Growth Factor, Heparin, Hippocampus, Male, Mice, Inbred Strains, Neurons, Fibroblast Growth Factor 2, Dentate Gyrus, Intercellular Signaling Peptides and Proteins, Mice, Heparin-binding EGF-like Growth Factor
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