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Reconstruction of disturbed brain function with neural stem cells from the investigation of the mechanism and induction to neuronal differentiation by trophic factor

Research Project

Project/Area Number 16500203
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionNagoya City University

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)

Co-Investigator(Kenkyū-buntansha) NISHINO Hitoo  Nagoya City University, Graduate School of Medical Sciences, President, 学長 (60073730)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
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)
Keywordsembryonic 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
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.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (30 results)

All 2007 2006 2005 2004 Other

All Journal Article (30 results)

  • [Journal Article] Clioquinol administration attenuates motor dysfuntion after small hemorrhage near tinternal capsule in rats2007

    • Author(s)
      Masuda T., Hida H., Kanda Y, Aihara N, Kengo Ohta, Yamada K, Nishino H
    • Journal Title

      Journal Neuroscience Research 85(1)

      Pages: 213-222

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Environmental enrichment brings a beneficial effect on beam walking and enhancest migration of doublecortin-positive cells following striatal lesions in rats.2007

    • Author(s)
      Urakawa, S, Hida H., Masuda T, Misumi S, Kim T-S, Nishino H
    • Journal Title

      Neuroscience 144(3)

      Pages: 920-933

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pleiotrophin promotes functional recovery after neural transplantation in rats2007

    • Author(s)
      Hida H, Masuda T, Sato T, Kim TS, Misumi S, Nishino H
    • Journal Title

      Neuroreport 18(2)

      Pages: 179-183

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Clioquinol administration attenuates motor dysfuntion after small hemorrhage near the internal capsule in rats2007

    • Author(s)
      Masuda T., Hida H., Kanda Y, Aihara N, Ohta K, Yamada K, Nishino H
    • Journal Title

      J Neurosci Res 85

      Pages: 213-222

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.2007

    • Author(s)
      Urakawa S, Hida H., Masuda T., Misumi S., Kim T-S., Nishino H.
    • Journal Title

      Neuroscience 144

      Pages: 920-933

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pleiotrophin promotes functional recovery after neural transplantation in rats2007

    • Author(s)
      Hida H, Masuda T, Sato T, Kim TS, Misumi S, Nishino H.
    • Journal Title

      Neuroreport 17(2)

      Pages: 179-183

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Clioquinol administration attenuates motor dysfuntion after small hemorrhage near the internal capsule in rats2007

    • Author(s)
      Masuda T., Hida H., Kanda Y, Aihara N, Kengo Ohta, YamadaK, Nishino H
    • Journal Title

      J Neurosci Res 85・1

      Pages: 213-222

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.2007

    • Author(s)
      Urakawa, S, Hida H., Masuda T, Misumi S, Kim T-S, Nishino H
    • Journal Title

      Neuroscience 144・3

      Pages: 920-933

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pleiotrophin promotes functional recovery after neural transplantation in rats2007

    • Author(s)
      Hida H, Masuda T, Sato T, Kim TS, Misumi S, Nishino H.
    • Journal Title

      Neuroreport 18・2

      Pages: 179-183

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Treatment with deferoxamine increases neurons from neural stem/progenitor cells2006

    • Author(s)
      Kim H-J., Hida H., Jung C-G, Miura Y., Nishino H.
    • Journal Title

      Brain Resarch 1092

      Pages: 1-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of nitric oxide for the 3-nitropropionic acid-induced striatal toxicity in rats2006

    • Author(s)
      Deshpande, S.B., Hida, H., Takei, N., Masuda, T., Baba, H., Nishino, H.
    • Journal Title

      Brain Research 1108

      Pages: 205-215

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Treatment with deferoxamine increases neurons from neural stem/progenitor cells2006

    • Author(s)
      KimH-J., HidaH., JungC-G, MiuraY., Nishino H.
    • Journal Title

      Brain Res. 1092

      Pages: 1-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of nitric oxide for the 3- nitropropionic acid-induced striatal toxicity in rats.2006

    • Author(s)
      Deshpande, S.B., Hida, H, Takei, N., Masuda, T., Baba, H.Nishino, H.
    • Journal Title

      Brain Res. 1108

      Pages: 205-215

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Treatment with deferoxamine increases neurons from neural stem/progenitor cells2006

    • Author(s)
      Kim H-J., Hida H., Jung C-G, Miura Y., Nishino H.
    • Journal Title

      Brain Research 1092

      Pages: 1-15

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Involvement of nitric oxide for the 3-nitropropionic acid-induced striatal toxicity in rats2006

    • Author(s)
      Deshpande, S.B., Hida, H, Takei, N., Masuda, T., Baba, H., Nishino, H.
    • Journal Title

      Brain Research 1108

      Pages: 205-215

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 線条体の幹細胞分化因子2005

    • Author(s)
      飛田秀樹, 鄭 且均, 西野仁雄
    • Journal Title

      Clinical Neuroscience 44(7)

      Pages: 487-492

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiation2005

    • Author(s)
      Jung C-G, Kim H-J, Kawaguchi M, Khanna KK, Hida H., Asai K, Nishino H, Miura Y.
    • Journal Title

      Development 132(23)

      Pages: 5137-5145

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 神経移植におけるプレイオトロプィンの効果2005

    • Author(s)
      飛田秀樹
    • Journal Title

      脳神経外科ジャーナル 14(8)

      Pages: 487-492

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differentiation factor for stem cells in the striatum2005

    • Author(s)
      Hida H, Jung CG, Nishino H.
    • Journal Title

      Clinical Neuroscience 44(7)

      Pages: 487-492

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiation2005

    • Author(s)
      Jung C-G, Kim H-J, Kawaguchi M, Khanna KK, Hida H, Asai K, Nishino H, Miura Y.
    • Journal Title

      Development 132(23)

      Pages: 5137-5145

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より2005

    • Author(s)
      Hida H.
    • Journal Title

      Jpn J Neurosurgery 14(8)

      Pages: 487-492

    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Homeotic factor ATBF 1 induces the cell cycle arrest associated with neuronal differentiation2005

    • Author(s)
      Jung C-G, Kim H-J, Kawaguchi M, Khanna KK, Hida H, Asai K, Nishino H, Miura Y.
    • Journal Title

      Development 132(23)

      Pages: 5137-5145

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 神経移植におけるプレイオトロフィンの効果2005

    • Author(s)
      飛田 秀樹
    • Journal Title

      脳神経外科ジャーナル 14(8)

      Pages: 487-492

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PleiotrophinmRXA is highly expressed in neural stem (progenitor) cells of mouse ventral mesencephalon and the product promotes production of dopaminergic neurons from ES cell-derived nestin-positive cells2004

    • Author(s)
      Jung CG, Hida H, Nakahira K, Ikenaka K, Kim H-J, Nishino H
    • Journal Title

      FASEB Journal 18(11)

      Pages: 1237-1239

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pleiotrophin mRNA is highly expressed in neural stem (progenitor) cells of mouse ventral mesencephalon and the product promotes production of dopaminergic neurons from ES cell-derived nestin-positive cells2004

    • Author(s)
      Jung C-G, Hida H., Nakahira K., Ikenaka K., Kim H-J, Nishino H.
    • Journal Title

      FASEB J 18(11)

      Pages: 1237-1239

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pleiotrophin mRNA is highly expressed in neural stem (progenitor) cells of mouse ventral mesen cephalon and the product promotes production of dopaminergic neurons from ES cell-derived nestin-positive cells2004

    • Author(s)
      Jung CG, Hida H, Nakahira K, Ikenaka K, Kim H-J, Nishino H.
    • Journal Title

      FASEB J. 18(11)

      Pages: 1237-1239

    • Related Report
      2004 Annual Research Report
  • [Journal Article] High titer retroviral gene transduction to neural progenitor cells for establishment of donor cells in neural transplantation to parkinsonian model rats.2004

    • Author(s)
      Kodama Y, Hida H, Jung C-G, Baba H, Isono M, Kobayashi H, Nishino H.
    • Journal Title

      Neurol Med Chr(Tokyo) 44(7)

      Pages: 344-351

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 線条体の幹細胞分化因子2004

    • Author(s)
      飛田秀樹, 鄭 且均, 西野仁雄
    • Journal Title

      Clinical Neuroscience 23(3)

      Pages: 284-286

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Treatment with deferoxamine increases neurons from neural stem/progenitor cells

    • Author(s)
      Kim H-J., Hida H., Jung C-G, Miura Y., Nishino H.
    • Journal Title

      Brain Research (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel animal model for periventricular leukomalacia targeting late oligodendrocyte progenitors

    • Author(s)
      Mizuno K, Hida H, Ito H, Masuda T, Urakawa S, Togari H, Nishino H
    • Journal Title

      Nagoya Medical Journal (in press)

    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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