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Elucidation of pathological role of ERK in diabetic spine dysmorphogenesis and development of new drug therapy

Research Project

Project/Area Number 24790539
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionNihon University

Principal Investigator

YASUHIRO Kosuge  日本大学, 薬学部, 助教 (70383726)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords糖尿病 / 海馬 / シナプス / インスリン受容体 / スパイン / 17β-estradiol
Research Abstract

There is evidence that diabetes condition is associated with hippocampal impairment, although how this occurs is not clear. In this study we investigated pathological roles of ERK, an important component in the regulation of synaptic plasticity, in diabetes-induced spine dysmorphogenesis. The inhibition of ERK activity was observed in streptozotocin-induced diabetic mice and high glucose-treated neuron. Chronic high-glucose treatment impaired insulin signaling in vitro models of diabetes. Administration of 17beta-estradiol (E2) and its derivative (E2A) leaded to activation of ERK both in vivo and in vitro. These results suggest that Insulin receptor dysfunction may play a role in chronic hyperglycemia-induced hippocampal impairment, and that E2 is a promising therapeutic drug for diabetic spine dysmorphogenesis.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (11 results)

All 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] Protective effect of S-allyl-L-cysteine against endoplasmic reticulum stress- induced neuronal death is mediated by inhibition of calpain2014

    • Author(s)
      Imai T, Kosuge Y, Endo,. Umeda K, Miyagishi H, Ishige K, Makishima M, Ito Y
    • Journal Title

      Amino Acids

      Volume: 46(2) Pages: 385-393

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of S-allyl-L-cysteine against endoplasmic reticulum stress-induced neuronal death is mediated by inhibition of calpain.2014

    • Author(s)
      Imai T, Kosuge Y, Endo-Umeda K, Miyagishi H, Ishige K, Makishima M, Ito Y.
    • Journal Title

      Amino Acids.

      Volume: 46(2) Issue: 2 Pages: 385-393

    • DOI

      10.1007/s00726-013-1628-4

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 高グルコース処置がヒト神経芽腫細胞SH-SY5Yのシナプス形成に及ぼす影響2014

    • Author(s)
      1小菅康弘,端山真奈美,石毛久美子,伊藤芳久
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Year and Date
      2014-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] S-allyl-L-cysteineはCa^<2+> binding domainとの相互作用によりcalpain活性を抑制する2014

    • Author(s)
      2小菅康弘,今井徹,石毛久美子,伊藤芳久
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 成熟ニンニク由来成分S-allyl-L-cysteineはcalpainの活性化を阻害する2013

    • Author(s)
      3今井徹,小菅康弘,石毛久美子,伊藤芳久
    • Organizer
      第15回応用薬理シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2013-09-28
    • Related Report
      2013 Final Research Report
  • [Presentation] -allyl-L-cysteineの小胞体ストレス誘発神経細胞死抑制効果にはcalpain阻害作用が関与する2013

    • Author(s)
      4今井徹,小菅康弘,梅田香織,石毛久美子,槇島誠,伊藤芳久
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] S-allyl-L-cysteineの小胞体ストレス誘発神経細胞死抑制効果にはcalpain阻害作用が関与する2013

    • Author(s)
      今井 徹,小菅 康弘,梅田 香織, 石毛 久美子,槇島 誠, 伊藤 芳久
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 成熟ニンニク由来成分S-allyl-L-cysteineはcalpainの活性化を阻害する

    • Author(s)
      今井 徹、小菅 康弘、石毛 久美子、伊藤 芳久
    • Organizer
      第15回応用薬理シンポジウム
    • Place of Presentation
      コクヨホール(港区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] S-allyl-L-cysteineはCa2+-binding domainとの相互作用によりcalpain活性を抑制する

    • Author(s)
      小菅 康弘、今井 徹、石毛 久美子、伊藤 芳久
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Annual Research Report
  • [Presentation] 高グルコース処置がヒト神経芽腫細胞SH-SY5Yのシナプス形成に及ぼす影響

    • Author(s)
      小菅 康弘、端山 真奈美、石毛 久美子、伊藤 芳久
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.pha.nihon-u.ac.jp/pharmacol.html/

    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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