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Brain organoids as pathological model for Dravet syndrome applicable to drug discovery research

Research Project

Project/Area Number 18K15735
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionFukuoka University

Principal Investigator

TANAKA Yasuyoshi  福岡大学, てんかん分子病態研究所, ポスト・ドクター (50714466)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsDravet症候群 / 発達性てんかん性脳症 / SCN1A / Nav1.1 / 疾患特異的iPS細胞 / 脳オルガノイド / 病態モデル / GABA作動性神経細胞 / てんかん / iPS細胞 / 疾患モデル / 終脳オルガノイド / ex vivo病態モデル
Outline of Final Research Achievements

In this study, brain organoids in the medial ganglionic eminence (MGE) region containing neural stem cells positive for FOXG1 and NKX2.1 expression were developed from iPS cells derived from Dravet syndrome (DS) patients. The expression of parvalbumin (PV) positive inhibitory neurons was confirmed in brain organoids resembling in medial ganglionic eminence (MGE). It was also confirmed that these PV positive cells were positive for Nav1.1 expression.

Academic Significance and Societal Importance of the Research Achievements

てんかん等の脳神経機能異常を示す病態研究において、ヒト脳組織は利用できない。代わりにモデル動物を用いたin vivo研究が行われているが、必ずしもヒトの複雑な病態を反映しているとは言い難い。
本研究において、疾患特異的iPS細胞よりDSの病態と関連性のあるMGEOsの作製に成功した。これにより、患者の脳組織を模倣したex vivo病態モデルとして、病態の解明や新たな治療法の開発に向けた、今後のてんかん研究への応用が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2021 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Application of induced pluripotent stem cells in epilepsy2020

    • Author(s)
      Hirose Shinichi、Tanaka Yasuyoshi、Shibata Mami、Kimura Yuichi、Ishikawa Mitsuru、Higurashi Norimichi、Yamamoto Toshiyuki、Ichise Eisuke、Chiyonobu Tomohiro、Ishii Atsushi
    • Journal Title

      Molecular and Cellular Neuroscience

      Volume: 108 Pages: 103535-103535

    • DOI

      10.1016/j.mcn.2020.103535

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of human induced pluripotent stem cells derived from skin cells of a patient with Dravet syndrome.2020

    • Author(s)
      Kimura Y, Tanaka Y, Shirasu N, Yasunaga S, Higurashi N, Hirose S.
    • Journal Title

      Stem Cell Res.

      Volume: 47 Pages: 101857-101857

    • DOI

      10.1016/j.scr.2020.101857

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Basic study of pathogenesis of epilepsy by means of iPS cell2021

    • Author(s)
      Yasuyoshi TANAKA
    • Organizer
      the 13th Asian & Oceanian Epilepsy Congress (AOEC)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Physiological Characterization of neurons derived from Dravet syndrome iPSCs models.2019

    • Author(s)
      Y. Tanaka, M. Ishikawa, N. Higurashi, H. Okano, S. Hirose.
    • Organizer
      The 15th Asian and Oceania Congress of Child Neurology (15th AOCCN).
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] A MUTATION IN SCN1A SELECTIVELY IMPAIRS IPSCS-DERIVED INHIBITORY NEURONS DERIVED FROM A PATIENT WITH DRAVET SYNDROME.2019

    • Author(s)
      Y. Tanaka, M. Ishikawa, N. Higurashi, H. Okano, S. Hirose.
    • Organizer
      The International Society of Stem Cell Research 2019 Annual Meeting (ISSCR 2019).
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] MEAシステムを用いたDravet症候群患者iPS細胞由来神経細胞の機能解析.2019

    • Author(s)
      田中泰圭, 石川充, 日暮憲道, 岡野栄之, 廣瀬伸一.
    • Organizer
      第53回日本てんかん学会学術集会.
    • Related Report
      2019 Research-status Report
  • [Presentation] Scn1a KOマウス海馬由来抑制性神経細胞の機能解析.2019

    • Author(s)
      田中泰圭, モレイラ ケビン, 廣瀬伸一.
    • Organizer
      NEURO2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会).
    • Related Report
      2019 Research-status Report
  • [Presentation] In-Vitro Hippocampal Inhibitory Neuronal activity of SCN1A KO Mice and a Potential Alternative Treatment Path.2018

    • Author(s)
      K. Moreira, Y. Tanaka, S. Hirose.
    • Organizer
      the American Epilepsy Society annual meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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