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Neurotoxicity of anesthetics in the developing neurons: in vitro model to assess the neurotoxicity in human induced pluripotent stem cell derived neurons.

Research Project

Project/Area Number 25670666
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MAKITA Koshi  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (20199657)

Co-Investigator(Renkei-kenkyūsha) ITO Hiroyuki  東京医科歯科大学, 医学部附属病院, 助教 (80595554)
UCHIDA Tokujiro  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (40262183)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsiPS細胞由来神経細胞 / 麻酔薬 / 毒性評価 / ケタミン / ミトコンドリア / アポトーシス / iPS細胞 / 神経幹細胞 / 麻酔薬毒性 / 幼弱脳 / 活性酸素種
Outline of Final Research Achievements

To study the toxic effect of anesthetic drugs on human neurons, an experimental model using cultured neurons derived from human induced pluripotent stem cells (iPSCs) was examined, and the mechanisms of their toxicity were studied. We studied ketamine toxicity in this study, and we established an in vitro model to assess the neurotoxicity in iPSC-derived neurons. The present data indicate that initial mitochondrial dysfunction and autophagy may be resulted from inhibitory effect of ketamine on the mitochondrial electron transport system. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons, and these mechanisms underlie ketamine-induced neural toxicity.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (2 results)

All 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (1 results)

  • [Journal Article] Ketamine causes mitochondrial dysfunction in human induced pluripotent stem cell-derived neurons.2015

    • Author(s)
      Ito H, Uchida T, Makita K.
    • Journal Title

      PLOS ONE

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ヒト人工多能性幹細胞由来神経細胞を用いたケタミンの毒性評価:ミトコンドリア機能障害およびアポトーシス誘導に関する検討2015

    • Author(s)
      伊藤裕之、内田篤治郎、槇田浩史
    • Organizer
      日本麻酔科学会 第62回学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2015-05-28 – 2015-05-30
    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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