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

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16500203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Nagoya 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
• Keywords: embryonic stem cell / dopaminergic neuron / neuronal differentiation / neural stem cell / cell cycle / low oxygen / hupoxia inducible factor-1 / pleiotrophin

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.

Research Products

• [Journal Article] Clioquinol administration attenuates motor dysfuntion after small hemorrhage near tinternal capsule in rats (2007)
  • 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
• [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
• [Journal Article] Pleiotrophin promotes functional recovery after neural transplantation in rats (2007)
  • 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
• [Journal Article] Clioquinol administration attenuates motor dysfuntion after small hemorrhage near the internal capsule in rats (2007)
  • 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
• [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
• [Journal Article] Pleiotrophin promotes functional recovery after neural transplantation in rats (2007)
  • 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
• [Journal Article] Treatment with deferoxamine increases neurons from neural stem/progenitor cells (2006)
  • 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
• [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 Research 1108 Pages: 205-215
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Treatment with deferoxamine increases neurons from neural stem/progenitor cells (2006)
  • 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
• [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
• [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
• [Journal Article] Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiation (2005)
  • 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
• [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
• [Journal Article] Differentiation factor for stem cells in the striatum (2005)
  • 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
• [Journal Article] Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiation (2005)
  • 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
• [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
• [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 cells (2004)
  • 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
• [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 cells (2004)
  • 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