Fetal Alcohol Spectrum Disorder Pathogenesis Mechanisms Approached With Cell Species-Level Resolution

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15275
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kyoto University
• Principal Investigator: Okigawa Sayumi 京都大学, 医生物学研究所, 助教 (60883303)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 神経科学 / 胎児性アルコールスペクトラム障害 / マウス行動解析

Outline of Final Research Achievements

Drinking during pregnancy affects feta development and the brain and causes a group of conditions, called Fetal alcohol spectrum disorder (FASD). The FASD pathogenesis is still unknown and no treatment has been established. So the purpose of this study was to clarify the effects of alcohol on the fetal brain using FASD mice.
We created the FASD mice under the strict controlling of alcohol exposure. Using the mice, we performed behavioral experiments, facial evaluation by head CT and histological analysis of the brain. These were evaluated based on the diagnostic criteria of the human FASD guidelines. As a result, we succeeded in creating a model mouse that mimics human symptoms and behavioral levels based on the diagnostic criteria of the human FASD guidelines. And by establishing the above evaluation technique, we clarified the correlation between the amount of ethanol exposure to the fetus and behavioral abnormalities, as well as the effects on the brain.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

1800年代よりアルコールが及ぼす胎児への影響は問題視され、多くの研究がなされてきた
。しかし胎児へのアルコール移行濃度を詳細に評価した研究はこれまでに実施されていない。本研究はFASDマウスモデルを作製し、マウス胎仔へのアルコール移行量を、胎仔脳および血中サンプルより厳密に評価した。作製したモデルマウスはヒトFASDの診断基準になっているヒトの症状および行動レベルを模倣していることから、今後のFASD研究への汎用性が高い。胎仔へのエタノール暴露量の評価やFASD症状の評価技術は、疾患モデルマウス作製と評価への展開が期待されるため、科学的な意義に加え、医学および薬学的意義も高いと考える。