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Development of factors that prevent secondary neuronal degeneration

Research Project

Project/Area Number 11671370
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionEhime University

Principal Investigator

DESAKI Junzo  Ehime University, School of Medicine, Assistant Professor, 医学部, 講師 (00036451)

Co-Investigator(Kenkyū-buntansha) SATO Kohji  Hamamatsu University, School of Medicine, Professor, 教授 (80235340)
TANAKA Junya  Ehime University, School of Medicine, Professor, 医学部, 教授 (70217040)
SAKANAKA Masahiro  Ehime University, School of Medicine, Professor, 医学部, 教授 (60170601)
WEN Tong-chun  Ehime University, School of Medicine, Instructor, 医学部, 助手 (70284411)
榊 三郎  愛媛大学, 医学部, 教授 (30116933)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordssecondary neuronal degeneration / gerbil / hippocampus / prosaposin-related peptide / apoptosis / Bcl-x_L / passive avoidance experiment / 神経細胞の二次変性 / 一過性前脳虚血 / インターロイキン3 / エリスロポエチン / ジンセノサイドRb_1
Research Abstract

The 7-day infusion of a prosaposin-related 18-mer peptide (18-MP) into the lateral ventricle of gerbils starting 2 hours before or just after 3-min forebrain ischemia is known to prevent the occurrence of learning disability and neuronal death in the hippocampal CA1 field. However, it remains to be determined whether or not intracerebroventricular infusion of the 18-MP starting 72 hours after 3-min forebrain ischemia rescues hippocampal CA1 neurons, and the mechanism (s) by which the 18-MP exerts a protective effect on ischemic hippocampal CA1 neurons also remains to be determined. In the first set of the present experiments, gerbils were infused with the 18-MP for 28 days into the lateral ventricle at 72 hours after 3-min forebrain ischemia. 18-MP infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by the step-down passive avoidance task. Subsequent light microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus were significantly more numerous in gerbils infused with the 18-MP than in those receiving vehicle infusion. In the second set of the present experiments, the 18-MP prevented in vitro neuronal apoptosis or apoptotic neuron death caused by the nitric oxide (NO) donor sodium nitroprusside (SNP) in a concentration-dependent manner. Moreover, the 18-MP (1-10^5 fg/ml) increased the expression of Bcl-x_L, an antiapoptotic Bcl-2 family protein, in cultured neurons. Thus, the present study indicates that the 18-MP prevents secondary neuronal degeneration after ischemia in vivo possibly through an increase in the expression of the antiapoptotic factor, Bcl-x_L.

Report

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

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Chen Y-S et al.: "Effect of basic fibroblast growth factor (bFGF) -neutralizing antibody and platelet factor 4 on facial nerve regeneration."Experimental Neurology. 155. 274-283 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Igase K et al.: "An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia."J Cereb.Blood Flow Metab.. 19. 298-306 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujita H et al.: "Differential expressions of glycine transporter 1 and three glutamate transporter mRNAs in the hippocampus of gerbils with transient forebrain ischemia."J.Cereb.Blood Flow Metab.. 19. 604-615 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watanabe H et al.: "Increase in p53 protein expression following cortical infarction in the spontaneously hypertensive rat."Brain Res.. 837. 38-45 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakatsuka H et al.: "Release of cytochrome c from mitochondria to cytosol in gerbil hippocampal CA1 neurons after transient forebrain ischemia."Brain Res.. 849. 216-219 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 阪中雅広 ら: "脳卒中の克服:神経細胞保護因子の実用可能性"生体の科学. 51(1). 11-17 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakatsuka H et al.: "Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils."Neuroscience Letters. 278. 53-56 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakatsuka H et al.: "Histochemical cytochrome c oxidase activity and caspase-3 in gerbil hippocampal CA1 neurons after transient forebrain ischemia."Neuroscience Letters. 285. 127-130 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yang L et al.: "Improvement of the viability of cultured rat neurons by the non-essential amino acids L-serine and glycine that upregulates expression of the anti-apoptotic gene product Bcl-w."Neuroscience Letters. 295. 97-100 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chen Y-S et al.: "Effect of basic fibroblast growth factor (bFGF) -neutralizing antibody and platelet factor 4 on facial nerve regeneration."Experimental Neurology. 155. 274-283 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Igase K et al.: "An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia."J Cereb.Blood Flow Metab.. 19. 298-306 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujita H et al.: "Differential expressions of glycine transporter 1 and three glutamate transporter mRNAs in the hippocampus of gerbils with transient forebrain ischemia."J.Cereb.Blood Flow Metab.. 19. 604-615 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watanabe H et al.: "Increase in p53 protein expression following cortical infarction in the spontaneously hypertensive rat."Brain Res.. 837. 38-45 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakatsuka H et al.: "Release of cytochrome c from mitochondria to cytosol in gerbil hippocampal CA1 neurons after transient forebrain ischemia."Brain Res.. 849. 216-219 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakatsuka H et al.: "Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils."Neuroscience Letters. 278. 53-56 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakatsuka H et al.: "Histochemical cytochrome c oxidase activity and caspase-3 in gerbil hippocampal CA1 neurons after transient forebrain ischemia."Neuroscience Letters. 285. 127-130 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yang L et al.: "Improvement of the viability of cultured rat neurons by the nonessential amino acids L-serine and glycine that upregulates expression of the anti-apoptotic gene product Bcl-w."Neuroscience Letters. 295. 97-100 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 阪中雅広 ら: "脳卒中の克服:神経細胞保護因子の実用可能性"生体の科学. 51(1). 11-17 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakatsuka H et al.: "Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils."Neuroscience Letters,. 278. 53-56 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakatsuka H et al.: "Histochemical cytochrome c oxidase activity and caspase-3 in gerbil hippocampal CA1 neurons after transient forebrain ischemia."Neuroscience Letters,. 285. 127-130 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yang L et al.: "Improvement of the viability of cultured rat neurons by the non-essential amino acids L-serine and glycine that upregulates expression of the anti-apoptotic gene product Bcl-w."Neuroscience Letters,. 295. 97-100 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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