| Project/Area Number |
12557126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagoya University (2002)
Gifu Pharmaceutical University (2000-2001) |
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Principal Investigator |
NITTA Atsumi Nagoya University Hospital, Associate Professor, 医学部附属病院, 助教授 (20275093)
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| Co-Investigator(Kenkyū-buntansha) |
NABESHIMA Toshitaka Nagoya University Hospital, Professor, 医学部附属病院, 教授 (70076751)
NOMOTO Hiroshi Gifu Pharmaceutical Univ.Pharmacy Sciences Associate Professor, 薬学部, 助教授 (80164747)
FURUKAWA Shoei Gifu Pharmaceutical Univ.Pharmacy Sciences Professor, 薬学部, 教授 (90159129)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | Immunophilin liogands / neurotrophic factors / spinal cord damages / neuroprotective effects / neurodegenerations / 脳由来神経栄養因子 / グリア細胞株由来神経栄養因子 / T細胞 / マクロファージ / 酵素免疫測定法 / ラット / 遺伝子導入 |
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| Research Abstract |
FK506, one of the immunosuppressant drugs, has been recently reported to protect neuronal degeneration in the central nervous system, however, the mechanisms of action were not completely clarified. In this study, we investigated the effects of FK506 on the induction of glial cell line-derived neurotrophic factor (GDNF), and involvement of the induced GDNF in the protection against degeneration of dopaminergic neurons. Neurons cultured from embryonic rat hippocampus were cultured in the presence of FK506, and neuronal cell survival and concentration of GDNF in the medium were assessed. GDNF was measured by the specific and sensitive enzyme immunoassay (EIA). In vivo study, FK506 (1.5 mg/kg) was intraperitoneally administrated to mice with or without striatal injection of 6-OHDA. The content of GDNF in the various brain regions, and the degree of neuronal degeneration of striatum were then estimated by the EIA and their rotation behavior induced by methanphetamine, respectively.
FK506 elevated GDNF contents in the media conditioned with neurons in dose-dependent manners. FK506 simultaneously protected cultured neurons from the cell death. Further, peripheral administration of FK506 increased GDNF contents in the striatum of mice. The number of rotation induced by metanphetamin was reduced by the administration of FK506 in striatum lesioned mice. The increase of GDNF content and suppression of the number of rotation were well-correlated each other, suggesting protective effects of it on dopaminergic neurons.
In Conclusions, 1) FK506 protects dopaminegic degeneration through induction of GDNF in vivo and in virto. 2) Immnonosapressive drugs such as FK506 may be a candidate for a novel therapeutic agent for Parkinson's disease.
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