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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.
Pubmed ID: 28547849 RIS Download
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View all literature mentionsThis polyclonal targets Doublecortin
View all literature mentionsThis polyclonal targets Rabbit Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis monoclonal targets Ab-10E4 ab1-hs anti-HS H1890 anti-heparan sufate anti-heparan sulfate
View all literature mentionsThis polyclonal targets Laminin antibody produced in rabbit
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis monoclonal targets Phospho-GSK-3beta (Ser9)
View all literature mentionsThis monoclonal targets GSK-3beta (27C10) Rabbit mAb
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View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets Sulfatase 2 antibody
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View all literature mentionsThis unknown targets HES-1
View all literature mentionsThis polyclonal targets Rabbit Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis monoclonal targets Heparan Sulfate Proteoglycan 2
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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