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Development of drug evaluation system in cultured human iPSC derived neuronal network which evoked sleep-awake rhythm

Research Project

Project/Area Number 17K20111
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering and related fields
Research InstitutionTohoku Institute of Technology

Principal Investigator

SUZUKI IKURO  東北工業大学, 大学院工学研究科, 准教授 (90516311)

Co-Investigator(Kenkyū-buntansha) 辛島 彰洋  東北工業大学, 工学部, 准教授 (40374988)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
KeywordsiPS / 睡眠 / 覚醒 / アミン・コリン / 徐波 / LTD / 睡眠恒常性仮説 / MEA / ヒトiPS細胞由来ニューロン / 概日リズム / Neuromodulator / 微小電極アレイ / ヒトiPS細胞 / ニューロン / 睡眠覚醒リズム / 薬効評価
Outline of Final Research Achievements

The cross-regional neurons in the brainstem, hypothalamus, and thalamus regulate the central nervous system, including the cerebral cortex, in a sleep-wake cycle-dependent manner. A characteristic brain wave, called slow wave, of about 1 Hz is observed during non-REM sleep, and the sleep homeostasis hypothesis proposes that the synaptic connection of a neural network is weakened during sleep. In the present study, we found that sleep-wake states can be mimicked by cyclic neuromodulator administration and show that LTD-like phenomena can be induced by 1 Hz low-frequency stimulation (LFS) in in vitro human iPSC-derived neurons. These results could be applied in studies on the mechanism of slow waves during sleep or in an in vitro drug efficacy evaluation depending on sleep-wake state.

Academic Significance and Societal Importance of the Research Achievements

Neuromodulatorや電気刺激によって、ヒトiPS細胞由来ニューロンに睡眠・覚醒状態を惹起させる本研究成果は、睡眠中の徐波のメカニズム研究や生体現象を模倣した睡眠覚醒状態依存的なin vitro薬効評価に応用することができると考えられる。

Report

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

    (8 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) Book (1 results)

  • [Int'l Joint Research] Buck Institute(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Impact of sleep-wake-associated neuromodulators and repetitive low-frequency stimulation on human iPSC-derived neurons2019

    • Author(s)
      Remi Yokoi, Miho Okabe, Naoki Matsuda, Aoi Odawara, Akihiro Karashima, Ikuro Suzuki
    • Journal Title

      Frontiers in Neuroscience

      Volume: 未定 Pages: 1-15

    • DOI

      10.3389/fnins.2019.00554

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] in vitroヒトiPS細胞由来神経ネットワークへ睡眠・覚醒リズムを惹起させる為の基礎検討2019

    • Author(s)
      横井れみ, 松田直毅, 辛島彰洋,鈴木郁郎
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経伝達物質および電気刺激は培養ヒトiPS細胞由来神経ネットワークに睡眠・覚醒様リズムを惹起する2019

    • Author(s)
      横井れみ, 松田直毅, 辛島彰洋,鈴木郁郎
    • Organizer
      日本安全性薬理研究会 第10回学術年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト iPS 細胞由来中枢神経ネットワークに概日リズムを惹起させる為の基礎検討2018

    • Author(s)
      岡部美穂,石橋勇人,奥山夏輝,松田直毅,小田原あおい,辛島彰洋,鈴木郁郎
    • Organizer
      平成30年東北地区若手研究者研究発表会
    • Related Report
      2017 Research-status Report
  • [Presentation] in vitroヒトiPSC由来中枢神経ネットワークに睡眠・覚醒リズムを惹起させる為の基礎検討2017

    • Author(s)
      岡部美穂,小田原あおい,松田直毅,辛島彰洋,鈴木郁郎
    • Organizer
      平成29年 電気学会 電子・情報・システム部門大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 培養ヒトiPS細胞由来中枢神経ネットワークに睡眠・覚醒リズムを惹起させる為の基礎検討2017

    • Author(s)
      岡部美穂,石橋勇人,奥山夏輝,松田直毅,小田原あおい,辛島彰洋,鈴木郁郎
    • Organizer
      第 33 回ライフサポート学会大会
    • Related Report
      2017 Research-status Report
  • [Book] “ヒトiPS細胞由来神経細胞の機能評価と創薬応用”,創薬のための細胞利用技術の最新動向と市場,第Ⅱ編 創薬・新薬への応用,第2章 薬剤安全性評価への応用2018

    • Author(s)
      鈴木郁郎
    • Publisher
      シーエムシー・リサーチ
    • Related Report
      2018 Annual Research Report

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Published: 2017-07-21   Modified: 2020-03-30  

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