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

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K18010
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine; Eating habits
• Research Institution: Kyoto 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
• Keywords: 自閉症スペクトラム障害 / フラボノイド / iPS細胞

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.

Free Research Field

小児神経学

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。