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Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor‐2 signaling impairment in the aged neurogenic niche
Author(s) -
Yamada Taihei,
Kerever Aurelien,
Yoshimura Yusuke,
Suzuki Yuji,
aka Risa,
Higashi Kyohei,
Toida Toshihiko,
Mercier Frederic,
ArikawaHirasawa Eri
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14081
Subject(s) - extracellular matrix , fibroblast growth factor , heparan sulfate , microbiology and biotechnology , fibroblast , signal transduction , perlecan , chemistry , extracellular , medicine , endocrinology , biochemistry , biology , glycosaminoglycan , in vitro , proteoglycan , receptor
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.