| Project/Area Number |
14082210
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
OOHIRA Atsuhiko Institute for Developmental Research, Aichi Human Service Center, Dept. Perinatol., Department Head (20101074)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥56,000,000 (Direct Cost: ¥56,000,000)
Fiscal Year 2006: ¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2005: ¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2004: ¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2003: ¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2002: ¥11,200,000 (Direct Cost: ¥11,200,000)
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| Keywords | chondroitin sulfate / proteoglycan / neuroglycan C / neural stem cell / brain / proliferation / neurite extension / cell death / 中枢神経 / NGC(ニューログリカンC) / 遺伝子改変マウス / FGF-2 / ニューログリカンC(NGC) / ADAM / 神経系前駆細胞 / NGC / 神経前駆細胞 / ニューロカン / ホスファカン / 中枢神経回路 / 新生児 / 虚血 / 低酸素 |
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| Research Abstract |
Functions of chondroitin sulfate proteoglycans (CSPGs) in the central nervous system were investigated in the two ways; functional analyses of a brain-specific CSPG, neuroglycan C (NGC), that we originally found in the developing rat brain and chondroitin sulfate (CS) polysaccharides as a major microenvironmental molecule of cells in the brain.
I. Functions of neuroglycan C
Site-directed mutagenesis revealed that a CS chain was introduced to S^<123> of the mouse NGC core protein. In addition to this CS-attachment domain, the extracellular region of NGC contains two other unique domains; a cluster of acidic amino acids (AA-domain) and an epidermal growth factor-like domain (EGF-domain). Both CS- and AA-domains had a high affinity to midkine, a growth factor. Both AA- and EGF- domains have a promotive activity for neurite extension. EGF-domain promotes growth of cells with EGF-receptors. Mouse strains with low and no expressions of NGC were produced. These mice show behavioral abnormalities. All these findings indicate that NGC is a functional molecule in the central nervous system.
II. Functions of chondroitin sulfate polysaccharides
CS polysaccharides isolated and purified from developing rat brains promote fibroblast growth factor (FGF)-2-mediated proliferation of neural stem cells. Commercial preparations of CS, CS-B and CS-E, also promote FGF-2-mediated neural stem cell growth, suggesting that an iduronic acid-containing structure (B-structure) and an over sulfated structure formed by GalNAc-4,6-disulfate (E-structure) in the CS polysaccharides are involved in this promotion of neural stem cell growth. Additionally, CS-E protects neurons from glutamate-induced excitatory neural cell death, that occurs immediately after brain injuries. Thus, CS polysaccharide is a bioactive molecule in the brain.
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