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Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor-2 signaling impairment in the aged neurogenic niche.
- Source :
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Journal of neurochemistry [J Neurochem] 2017 Aug; Vol. 142 (4), pp. 534-544. Date of Electronic Publication: 2017 Jun 20. - Publication Year :
- 2017
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Abstract
- Adult neurogenesis in the subventricular zone of the lateral ventricle decreases with age. In the subventricular zone, the specialized extracellular matrix structures, known as fractones, contact neural stem cells and regulate neurogenesis. Fractones are composed of extracellular matrix components, such as heparan sulfate proteoglycans. We previously found that fractones capture and store fibroblast growth factor 2 (FGF-2) via heparan sulfate binding, and may deliver FGF-2 to neural stem cells in a timely manner. The heparan sulfate (HS) chains in the fractones of the aged subventricular zone are modified based on immunohistochemistry. However, how aging affects fractone composition and subsequent FGF-2 signaling and neurogenesis remains unknown. The formation of the FGF-fibroblast growth factor receptor-HS complex is necessary to activate FGF-2 signaling and induce the phosphorylation of extracellular signal-regulated kinase (Erk1/2). In this study, we observed a reduction in HS 6-O-sulfation, which is critical for FGF-2 signal transduction, and failure of the FGF-2-induced phosphorylation of Erk1/2 in the aged subventricular zone. In addition, we observed increased HS 6-O-endo-sulfatase, an enzyme that may be responsible for the HS modifications in aged fractones. In conclusion, the data revealed that heparan sulfate 6-O-sulfation is reduced and FGF-2-dependent Erk1/2 signaling is impaired in the aged subventricular zone. HS modifications in fractones might play a role in the reduced neurogenic activity in aging brains.<br /> (© 2017 International Society for Neurochemistry.)
- Subjects :
- Aging drug effects
Animals
Extracellular Matrix metabolism
Extracellular Signal-Regulated MAP Kinases metabolism
Female
Heparitin Sulfate metabolism
Male
Mice, Inbred C57BL
Aging physiology
Cell Proliferation drug effects
Fibroblast Growth Factor 2 metabolism
Heparitin Sulfate pharmacology
Lateral Ventricles drug effects
Neurogenesis drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 142
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28547849
- Full Text :
- https://doi.org/10.1111/jnc.14081