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Molecular mechanism analysis of synaptic dysfunction in a novel Alzheimer's disease model mouse

Research Project

Project/Area Number 17H07418
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Neurophysiology / General neuroscience
Research InstitutionNational Center for Geriatrics and Gerontology

Principal Investigator

MINAMI Ryunosuke  国立研究開発法人国立長寿医療研究センター, 認知症先進医療開発センター, 研究員 (90806895)

Research Collaborator TSUDA Leo  
Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsアルツハイマー病マウスモデル / シナプス機能 / 内耳有毛細胞 / 聴力 / アルツハイマー病 / マウス / 加齢性難聴 / 創薬開発
Outline of Final Research Achievements

Our group produced a novel mouse AD model, in which amyloid-beta (Aβ) with familial AD mutation was expressed at mouse auditory hair cells. Electrophysiological assessment indicated that those mice showed hearing impairment specifically against high-frequency sounds stimulation (>32 kHz) at 4-months-old (Omata et al., Aging, 2016).
To reach the molecular mechanism of hearing defects in this AD mouse model, we observed cochlear with immunohistochemical approaches. The result showed that there are no degeneration of cochlear hair cells and no decline in synaptic ribbon numbers at 5-months-old. We propose that synaptic disorders might be involved in the hearing defects in the novel mouse AD model.

Academic Significance and Societal Importance of the Research Achievements

これまで, 多くの ADマウスモデルが開発され, 発症機序の解明から創薬研究まで広範にわたり用いられてきたが, 「疾患修飾薬」の開発には至っていない. 本研究課題を通して, 創薬研究から眺めた既存 ADマウスモデルの限界点を克服したこの新規モデルを用いた発症機序の解析からは, 前シナプスにおけるシナプス小胞リサイクリングの重要性を示唆する結果が得られた. 新規ADマウスモデルは, ADにおけるシナプス機能低下のメカニズムを分子レベルで解析するのに優れた系であることに留まらず, ADにおけるシナプス機能低下を聴力低下として定量化できることから薬剤開発に大いに貢献することも期待される.

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (5 results)

All 2018 2017

All Presentation (5 results)

  • [Presentation] 新規アルツハイマー病(AD)モデルマウスにおける神経機能低下分子メカニズム解析2018

    • Author(s)
      南竜之介, 林永美, 津田玲生
    • Organizer
      第37回 日本認知症学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Molecular commonalities between auditory hair cells and neurons in the study of age-related neuronal disorder2018

    • Author(s)
      Ryunosuke Minami, Young-Mi Lim, Leo Tsuda
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Molecular commonalities between auditory hair cells and neurons in the study of age-related neuronal disorder2018

    • Author(s)
      Ryunosuke Minami, Young-Mi Lim, Leo Tsuda
    • Organizer
      The 11th NAGOYA Global Retreat
    • Related Report
      2018 Annual Research Report
  • [Presentation] Molecular mechanism of hearing loss in a new mouse Alzheimer’s disease (AD) model2018

    • Author(s)
      Ryunosuke Minami, Young-Mi Lim, Leo Tsuda
    • Organizer
      The 10th NAGOYA Global Retreat
    • Related Report
      2017 Annual Research Report
  • [Presentation] ケミカルバイオロジーによるアルツハイマー病 (AD) 治療薬の開発研究2017

    • Author(s)
      南竜之介, 林永美, 津田玲生
    • Organizer
      第36回 日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report

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Published: 2017-08-25   Modified: 2020-03-30  

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