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Luteolin attenuates interleukin-6-mediated astrogliosis in human iPSC-derived neural aggregates: A candidate preventive substance for maternal immune activation-induced abnormalities

Research Project

Project/Area Number 17K18010
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Embryonic/Neonatal medicine
Eating habits
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

yoshida michiko  京都府立医科大学, 医学(系)研究科(研究院), 助教 (70754571)

Research Collaborator Zuiki Masashi  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords自閉症スペクトラム障害 / フラボノイド / iPS細胞 / 食と栄養
Outline of Final Research Achievements

Maternal infection during pregnancy increases the risk of autism spectrum disorders in offspring. Among animal studies, prenatal exposure to interleukin-6 (IL-6) has been associated with autism, though such findings remain to be elucidated in humans. We developed a human cell-based model of maternal immune activation (MIA) by exposing human induced pluripotent stem cells-derived neural aggregates to IL-6 and investigated whether luteolin; a naturally occurring flavonoid found in edible plants; could prevent MIA-induced abnormalities.
Luteolin treatment counteracted IL-6-mediated increases of astrocytes, reductions of neurons and increases of STAT3 phosphorylation. Our observations suggest that the flavonoid luteolin may attenuate or prevent MIA-induced neural abnormalities. As we observed increased apoptosis at high concentrations of luteolin, further studies are required to determine the optimal intake dosage and duration for pregnant women.

Academic Significance and Societal Importance of the Research Achievements

「母体感染によって生まれてくる子が発症する自閉症スペクトラム障害」に対し、発症予防効果を持ち、安全で妊婦も安心して摂取できる食品成分の探索を行った。候補として、炎症性サイトカインの産生抑制効果が報告されているフラボノイドと多価不飽和脂肪酸に着目し、フラボノイドの一種であるルテオリンが表現型を回復することを示した。

Report

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

    (1 results)

All 2017

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

  • [Journal Article] Luteolin attenuates interleukin-6-mediated astrogliosis in human iPSC-derived neural aggregates: A candidate preventive substance for maternal immune activation-induced abnormalities2017

    • Author(s)
      Zuiki Masashi、Chiyonobu Tomohiro、Yoshida Michiko、Maeda Hiroshi、Yamashita Satoshi、Kidowaki Satoshi、Hasegawa Tatsuji、Gotoh Hitoshi、Nomura Tadashi、Ono Katsuhiko、Hosoi Hajime、Morimoto Masafumi
    • Journal Title

      Neuroscience Letters

      Volume: 653 Pages: 296-301

    • DOI

      10.1016/j.neulet.2017.06.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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