| Project/Area Number |
17500267
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
SANGO Kazunori Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 東京都神経科学総合研究所, 副参事研究員 (50291943)
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| Co-Investigator(Kenkyū-buntansha) |
KAWANO Hitoshi Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 東京都神経科学総合研究所, 副参事研究員 (20161341)
HORIE Hidenori Waseda University, Organization for General Research, Professor, 総合研究機構, 教授 (80046135)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | axonal regeneration / galectin-1 / ciliary neurotrophic factor / phosphacan / neuronal cell culture / dorsal root ganglion neurons / Schwann cells / signal transduction / 脊髄後根神経節細胞 / マクロファージ / 網膜 |
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| Research Abstract |
We investigated the action mechanisms of growth-promoting molecules such as oxidized galectin-1 and ciliary neurotrophic factor (CNTF) and regulatory molecules such as chondroitin sulfate proteoglycans (especially phosphacan) in axonal regeneration after injury.
(1)Galectin-1 and CNTF : Immunohistochemistry on the sections of adult rat dorsal root ganglia (DRG) revealed that galectin-1 was abundantly expressed in small-diameter sensory neurons and Schwann cells while CNTF expression was restricted to Schwann cells. In contrast to the findings in vivo, we observed intense immunoreactivity for both galectin-1 and CNTF in DRG neurons after 3 hours, 2 days and 7 days in culture. At later stages of culture, the immunoreactivity was detected in regenerating neurites. These results suggest that both molecules are synthesized and transported to neurites in cultured DRG neurons. In spite of lacking signal leading sequences, galectin-1 is likely to be externalized from intact DRG neurons and Schw
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ann cells through the non-classical secretory pathway, whereas CNTF appears to be released from disrupted Schwann cells after peripheral nerve injury. Galectin-1 converted from the reduced form to the oxidized form in the extracellular space is likely to stimulate macrophages to secrete several factors (e.g. interleukin-6, bran derived neurotrophic factor), while CNTF directly acts on DRG neurons to activate signal transduction pathways (e.g. JAK-STAT3, MEK-MAPK, PI3K-Akt).
(2)Chondroitin sulfate proteoglycans : Phosphacan purified from embryonic (E20) or postnatal (P7, P20) rat brain impaired attachment and neurite outgrowth of cultured adult rat DRG neurons. These inhibitory effects were dependent on dose (10μg/ml>1μg/ml>>0.1μg/ml) and age of rats from which the molecule was purified (P20>P7>E20). Since the structure of chondroitin sulfate of these preparations are immunologically and compositionally different, these findings suggest that variation of chondroitin sulfate chains plays important roles in the regulatory actions of phosphacan. Less
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