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Analyses on the acceleration mechanism of vascular dementia by chronic stress

Research Project

Project/Area Number 21790639
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionNational Institute for Longevity Sciences,NCGG

Principal Investigator

KUNIMOTO Shohko  独立行政法人国立長寿医療研究センター, 加齢健康脳科学研究部, 流動研究員 (30350135)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsストレス / 脳血管性認知症 / CADASIL / 動物モデル / Notch3 / 血管性認知症モデル動物 / 遺伝環境相互作用
Research Abstract

CADASIL is the most common hereditary small vessel disease that is characterized by recurrent subcortical ischemic strokes and ultimately vascular dementia. It is linked to dominant mutations in the human NOTCH3 gene, which is primarily expressed in vascular smooth muscle cells (VSMCs) of the vessel wall. Pathogenic mechanisms remain unclear by the lack of a good animal model. Here, we generated a knock-in (KI) mouse model for one of the CADASIL mutations and investigated this mouse to elucidate whether the pathological hallmarks of CADASIL are observed with mutant Notch3. Further, we examined the effect of chronic intermittent restraint stress on the pathogenesis of CADASIL using this mouse.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (11 results)

All 2010 2009

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (6 results)

  • [Journal Article] Potent inhibitors of amyloid ss fibrillization, 4,5-dianilinophthalimide and staurosporine aglycone, enhance degradation of preformed aggregates of mutant Notch3.2010

    • Author(s)
      Takahashi K, Adachi K, Kunimoto S, Wakita H, Takeda K, Watanabe A
    • Journal Title

      Biochemical and Biophysical Research Communications 402

      Pages: 54-58

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in NOTCH3 cause the formation and retention of aggregates in the endoplasmic reticulum, leading to impaired cell proliferation.2010

    • Author(s)
      Takahashi K, Adachi K, Yoshizaki K, Kunimoto S, Kalaria NR, Watanabe A
    • Journal Title

      Human Molecular Genetics 19

      Pages: 79-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic stress-mutated presenilin 1 gene interaction perturbs neurogenesis and accelerates neurodegeneration.2010

    • Author(s)
      Kunimoto S, Nakamura S, Wada K, Inoue T
    • Journal Title

      Experimental Neurology 221

      Pages: 175-185

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potent inhibitors of amyloid β fibrillization, 4,5-dianilinophthalimide and staurosporine aglycone, enhance degradation of preformed aggregates of mutant Notch3.2010

    • Author(s)
      Takahashi K, Adachi K, Kunimoto S, Wakita H, Takeda K, Watanabe A
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 402 Pages: 54-58

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in NOTCH3 cause the formation and retention of aggregates in the endoplasmic reticulum, leading to impaired cell proliferation.2010

    • Author(s)
      Takahashi K, Adachi K, Yoshizaki K, Kunimoto S, Kalaria N R, Watanabe A
    • Journal Title

      Human Molecular Genetics 19

      Pages: 79-89

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] CADASILモデルとしての変異NOTCH3ノックインマウスの作製と解析2010

    • Author(s)
      國本正子
    • Organizer
      第33回日本神経科学大会
    • Place of Presentation
      神戸コンベンションセンター国際会議場
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] CADASIL モデルとしての変異NOTCH3ノックインマウスの作製と解析2010

    • Author(s)
      國本正子、渡邉淳、足立香代、松崎三記子、武田和也、脇田英明、Rajech N Kalaria、丸山和佳子、高橋慶吉
    • Organizer
      第33回日本神経科学大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] Proteomic analysis of the mutant Notch3-expressing cells and the microvessels of CADASIL brain2010

    • Author(s)
      渡邊淳、國本正子、足立香代、武田和也、新飯田俊平、脇田英明、Rajech N.Kalaria、高橋慶吉
    • Organizer
      ICAD 10 -Alzheimer's Association International Conference on Alzheimer's Disease 2010
    • Place of Presentation
      ホノルル
    • Related Report
      2010 Final Research Report
  • [Presentation] 家族性脳血管性認知症(CADASIL)モデル動物の作製と病態解析2009

    • Author(s)
      國本正子
    • Organizer
      第28回日本認知症学会
    • Place of Presentation
      東北大学百周年記念会館(宮城県)
    • Year and Date
      2009-11-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] 変異Notch3による重合体の形成と細胞増殖の低下2009

    • Author(s)
      渡邉淳、足立香代、國本正子、武田和也、脇田英明、高橋慶吉
    • Organizer
      第28回日本認知症学会学術集会
    • Place of Presentation
      仙台
    • Related Report
      2010 Final Research Report
  • [Presentation] 家族性脳血管性認知症(CADASIL)モデル動物の作製と病態解析2009

    • Author(s)
      國本正子、足立香代、吉崎嘉一、武田和也、脇田英明、高橋慶吉、渡邉淳
    • Organizer
      第28回日本認知症学会学術集会
    • Place of Presentation
      仙台
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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