| Project/Area Number |
19300132
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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 | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
SAKAGUCHI Kazushige Wakayama Medical University, 先端医学研究所, 教授 (60178548)
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| Co-Investigator(Kenkyū-buntansha) |
MIWA Hideto 和歌山県立医科大学, 医学部, 准教授 (50231626)
MIYAJIMA Masayasu 和歌山県立医科大学, 医学部, 助教 (80137257)
SAWADA Takahiro 和歌山県立医科大学, 先端医学研究所, 助教 (00382325)
JING Shuefeng 和歌山県立医科大学, 先端医学研究所, 助教 (70316123)
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| Project Period (FY) |
2007 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2007: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
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| Keywords | エフリン / パーキンソン病 / 神経幹細胞 / ラット / 再生医学 / Eph / ephrin / 再生医療 / マーモセット / ephrin(エフリン) |
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| Research Abstract |
Adult mouse brain has two neurogenic areas that contain neural stem/progenitor cells (NSPC). They can differentiate to nerve cells, astrocytes, and oligodendrocytes. Recent studies demonstrated that neural stem cells in the subventricular zone send extensions to the lateral ventricle and receive signals. Parkinson's disease, a neurodegenerative disorder, can be treated by supplying dopamine to improve symptoms, but this cannot be a curative treatment. Sooner or later, the dopaminergic neurons degenerate and become incapable of produce dopamine, resulting in deterioration of symptoms. Fetal nigral tissue transplantation can be one of the candidates of curative treatment, but is not regarded as a standard method due to ethical problems and difficulty in obtaining enough amount of such tissue. ES cells and iPS cells can be differentiated to dopaminergic cells, but the extent of differentiation and occasional occurrence of tumors must be controlled before applying to human. Immuno-rejectiv
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e reactions and ethical problems must be controlled. Degeneration of neurons in the nigrostriatal tract deplete striatal dopamine and causes Parkinson's disease. Striatum is located close to the lateral ventricle, suggesting that the subventricular neural stem cells are the good candidates for the treatment of this disease by causing proliferation, migration and differentiation. In the current project, we examined whether Eph/ephrin signaling system can be used to induce these phenomenon for the treatment of Parkinson's disease in rats and marmosettes. In rats, injection of clustered ephrin-A1 into the lateral ventricle could induce NSPC proliferation, migration and differentiation to dopaminergic neurons, and angiogenesis in the striatum. These effects resulted in behavioral improvement of rats with hemilateral nigrostriatal lesion. The histological and behavioral improvement lasted at least for 12 weeks. Marmosettes have so small a ventricle that it was difficult to inject clustered ephrin-A1 into the lateral ventricle. However, multiple injection of ephrin-A1 in and around the lateral ventricle improved the animal behavior as measured by Supermex. Recombinant ephrin-A1 fused with the coiled-coil domain of cartilage oligomeric matrix protein was produced in E. coli, but the product was not soluble and precipitated in water, probably due to formation of large multimers. Because of these results, we used the authentic method of clustering ephrin-A1-Fc by anti-IgG(Fc) antibody. Less
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