| Project/Area Number |
08680829
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Tokyo Metropolitan Institute for Neuroscience |
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Principal Investigator |
TANUMA Naoyuki Tokyo Metropolitan Inst.for Neurosci., 神経病理学研究部門, 研究員 (00281676)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAZOE Yoko Tokyo Metropolitan Inst.for Neurosci., 神経病理学研究部門, 主任研究員 (60281705)
KOJIMA Takashi Tokyo Metropolitan Inst.for Neurosci., 神経病理学研究部門, 主任研究員 (30225429)
MATSUMOTO Yoh Tokyo Metropolitan Inst.for Neurosci., 神経病理学研究部門, 副参事研究員 (90173921)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | EAE / Cytokine / Competitive PCR / tumor necrosis factor alpha / interferon gamma / transforming growth factor beta1 / interleukin 10 / Tumor necrosis factor / interferon-γ / Transforming growth factor-β1 / Interleukin-10 / competitivePCR / サイクロスポリンA |
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| Research Abstract |
To know the role of cytokines in neuroimmunological disorders, acute and chronic relapsing autoimmune encephalomyelitis (EAE) was induced in rats and the level of pro-and anti-inflammatory cytokine mRNA in the central nervous system (CNS) was quantitated by competitive PCR.In acute EAE,TNF-alpha and IFN-gammamRNA were detected mainly at the early stage of the disease, while one of anti-inflammatory cytokines, TGF-beta1, peaked at the later stage. IL-10 mRNA was elevated only at the early stage. In chronic relapsing EAE induced in Lewis rats with cyclosporin (CsA-EAE) and DA rats (DA-EAE), TNF-alpha mRNA was always up-regulated during the first and second attacks suggesting that this cytokine is essential for the initiation of EAE.IFN-gamma, which was suppressed at the first attack of CsA-EAE,would not be important for this process. Rather, IFN-gamma may an important role at the later stage since intraventricular injection at the preclinical stage induced more relapses or a chronic persistent form of the disease. With regard to anti-inflammatory cytokines, both TGF-beta1 and IF-10 mRNA were detected at all time points of CsA-EAE,whereas these anti-inflammatory cytokines were expressed at low levels during the first attack and were elevated at the second attack in DA-EAE.These results suggest that the relapse of DA-EAE was induced by the suppression of anti-inflammatory cytokines during the first attack of the disease. Taken together, the clinical course of chronic relapsing EAE is differentially regulated by pro- and anti-inflammatory cytokines.
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