| Project/Area Number |
16500203
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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 |
Neuroscience in general
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| Research Institution | Nagoya City University |
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Principal Investigator |
HIDA Hideki Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院医学研究科, 准教授 (00305525)
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| Co-Investigator(Kenkyū-buntansha) |
NISHINO Hitoo Nagoya City University, Graduate School of Medical Sciences, President, 学長 (60073730)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | embryonic stem cell / dopaminergic neuron / neuronal differentiation / neural stem cell / cell cycle / low oxygen / hupoxia inducible factor-1 / pleiotrophin / 胚性幹(ES)細胞 / チロシン水酸化酵素 / p27^<kip1> / HIF-1α / cdk5 / cytokine / LIF / wnt5a / 低酸素条件 / 細胞培養濃度 / ドパミンニューロン / IL-1b / Wnt 5a |
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| Research Abstract |
We investigate 1) how to increase of the number of dopaminergic (DAergic) neurons from embryonic stem (ES) cell-derived neural stem cells (NSCs) and 2) the mechanism of DAergic differentiation, and we also carried out basic research for neural transplantation using NSCs for the recovery of disturbed brain function. Data are summarized as follows.
1) DAergic differentiation from NSCs are induced by low physiological oxygen in the fetal brain (3.5% 02) or cytokine mixture (IL-113, IL-11, LIF, GDNF) which is enhanced in DA-depleted striatum. 2) Cell cycle inhibition in G 1/S phase by the pre-treatment with deferoxamine (DFO) induced neuronal differentiation relating to prolonged p27^<kiP1> elevation and activation of the neuroD signaling pathway. 3) DAergic differentiation induced by pleiotrophin (PTN), IL-1β and 3.5% oxygen is mediated by the mechanism relating to enhanced expression of HIF-1 a. 4) Investigation for the question if PTN promotes the survival of grafted cells clearly reveals that PTN treatment to donor cells promotes cell survival in the striatum after transplantation in which most grafted cells are close to cell death, resulting in better functional recovery.
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