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Prevention of injured neuron death by adennovirus vector.

Research Project

Project/Area Number 10470001
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionASAHIKAWA MEDICAL COLLEGE

Principal Investigator

KIYAMA Hiroshi  Asahikawa Medical College, Faculty of Medicine, Professor, 医学部, 教授 (00192021)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsNeuronal cell death / Regeneration / Neurite elongation / Hypoglossal nerve / Nerve injury / Adenovirus / Gene transfer / 遺伝子導入 / TC10 / GDNF / 軸策伸展 / アデノウィルス / 神経細胞死 / Cre-LoxP / 細胞死防御 / 運動ニューロン
Research Abstract

In an attempt to explore the molecular basis of nerve regeneration process, we have employed differential display-PCR to identify genes whose mRNA expression were up-regulated in injured hypoglossal motor neurons, and succeeded in isolating both novel as well as known molecules with possible association with neuronal survival and regeneration. To rescue or repair injured neurons, the adenovirus mediated gene transfer is one of intriguing means. We thus attempted to establish adenovirus mediated gene transfer system using rat. After establishing the gene transfer system specific to injured motor neurons, we have revealed distinct functional differences between two signaling pathways (P13K-mediated and ERK-mediated pathways downstream growth factor receptors) using our adenovirus system. In addition, we have also revealed a novel activity of Akt on neurite elongation both in vitro and in vivo. Functional significance of other molecules are also revealed by using this adenovirus mediated gene transfer system. For instance a novel Rho family protein TC10 was proved to have a function on neurite elongation. The results obtained in the present project provide useful tool for the nerve regeneration studies, in which the function of a certain molecule are examined in experimental animal, and also open up a possibility of therapeutic intervention in clinical conditions like brain trauma, ischaemia, or neurodegenerative conditions like ALS, Parkinson's disease, etc.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Toki H: "Enhancement of extracellular glutamate scavenge system in injured motoneurons."J.Neurochem.. 71. 913-919 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Namikawa K: "Enhanced expression of Raf-1 activator, 14-3-3, in injured motoneurons."Mol.Brain Res.. 55. 315-320 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mansur K: "Up-regulation of thioredoxin in motor neurons after nerve injury."Mol.Brain Res.. 62. 86-91 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujino H: "Discordant expression of c-Ret and GDNF receptor alpha-1 mRNAs in response to motor nerve injury in neonate rats."Mol.Brain Res.. 70. 298-303 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagomi S: "DDAH as a nerve injury associated molecule : The mRNA localization in the rat brain and its coincident up-regulation with nNOS in axotomized motor neurons."Eur.J.Neurosci.. 11. 2160-2166. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe K: "Expressed-sequence-tag approach to identify differentially expressed genes following peripheral nerve axotomy."Mol.Brain Res.. 64. 34-40. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuzaki H: "Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide i primary hippocampal neurons."J.Neurochem. 73. 2037-2046 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe K: "The small GTP-binding protein TC10 promotes growth cone-like formation and nerve elongation in neuronal cells, and its expression is induced."J.Neurosci.. 20. 4138-4144. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Namikawa K: "Akt/Protein kinase B prevents injury-induced motor neuron death and accelerates axonal regeneration."J.Neurosci.. 20. 2875-2886. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takano R: "Nerve growth factor protects oligodendrocytes from TNF-a-induced injury through Akt-mediated signaling mechanisms."J Biol Chem. 275. 16360-16365 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamaguchi A: "Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53."J Biol Chem. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toki H: "Enhancement of extracellular glutamate scavenge system in injured motoneurons."J.Neurochem.. 71. 913-919 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Namikawa K: "Enhanced expression of Raf-1 activator, 14-3-3, in injured motoneurons."Mol.Brain Res.. 55. 315-320 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mansur K: "Up-regulation of thioredoxin in motor neurons after nerve injury."Mol.Brain Res.. 62. 86-91 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujino H: "Discordant expression of c-Ret and GDNF receptor alpha-1 mRNAs in response to motor nerve injury in neonate rats."Mol.Brain Res.. 70. 298-303 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagomi S: "DDAH as a nerve injury associated molecule : The mRNA localization in the rat brain and its coincident up-regulation with nNOS in axotomized motor neurons."Eur.J.Neurosci.. 11. 2160-2166 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe K: "Expressed-sequence-tag approach to identify differentially expressed genes following peripheral nerve axotomy."Mol.Brain Res.. 64. 34-40 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuzaki H: "Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons."J.Neurochem. 73. 2037-2046 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe K: "The small GTP-binding protein TC10 promotes growth cone-line formation and nerve elongation in neuronal cells, and its expression is induced."J.Neurosci.. 20. 4138-4144 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Namikawa K: "Akt/Protein kinase B prevents injury-induced motor neuron death and accelerates axonal regeneration."J.Neurosci.. 20. 2875-2886 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takano R: "Nerve growth factor protects oligodendrocytes from TNF-a-induced injury through Akt-mediated signaling mechanisms."J Biol Chem. 275. 16360-16365 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamaguchi A: "Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53."J Biol Chem. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuzaki H: "Activation of Akt kinase Inhibits apoptosis and changes in Bcl-2 and Bax expressin Induced by nitric oxide in primary hippocampal neurons."J.Neurochem. 73. 2037-2046 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Namikawa K: "Akt/Protein kinase B prevents injury-induced motor neuron death and accelerates axonal regeneration."J.Neurosci.. 20. 2875-2886 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takano R: "Nerve growth factor protects oligodendrocytes from TNF-a-induced injury through Akt-mediated signaling mechanisms."J Biol Chem. 275. 16360-16365 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamaguchi A: "Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53."J Biol Chem. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kiryu-Seo S.: "Damage induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers"Proc. Natl. Acad. Sci. USA. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Namikawa K.: "Akt/PKB prevents injury-induced motor neuron death and accelerates axonal regeneration"J. Neurosci.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakagomi S: "Dimethylarginine dimethylaminohydrolase (DDAH) as a nerve injury associated molecule : The mRNA localization in the rat brain and its coincident up-regulation with neuronal NO synthase (nNOS) in axotomixed motor neurons"Eur. J. Neurosci.. 11. 2160-2166 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanabe K.: "Expressed-sequence-tag approach to identify differentially expressed genes following peripheral nerve axotomy"Mol. Brain Res.. 64. 34-40 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuzaki H.: "Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons"J. Neurochem. 73. (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toki H,: "Enhancement of extracellular glutamate scavenge system in injured motoneurons." J.Neurochem.71. 913-919 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanabe T,: "Alternative expression of Shc family members in nerve injured motoneurons." Mol.Brain Res.53. 292-297 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Namikawa K,: "Enhanced expression of Raf-1 activator,14-3-3,in injured motoneurons." Mol.Brain Res.55. 315-320

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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