Molecular basis underlying regulation of synapse-related protein expression and higher brain functions by maternal protein nutrition.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02158
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Kyushu University
• Principal Investigator: Furuya Shigeki 九州大学, 農学研究院, 教授 (00222274)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 発達期 / タンパク質栄養 / 精神疾患 / 統合失調症 / 遺伝子発現 / miRNA / RNA-seq

Outline of Final Research Achievements

This study aimed to reveal the effects of maternal protein restriction on mature brain function of F1 generation in terms of behavioral and molecular levels. In behavior, sensory information processing function was significantly affected in the female-restricted group-specific manner. Alterations in miRNA and mRNA expressions in the cerebral cortex was accompanied with the behavioral deficit in the female-restricted group. Bioinformatics analysis detected significant enrichments of the altered RNAs in biological processes involved in behavioral changes. Changes in the expression of synapse-related molecules such as neurotransmitter receptors and in hormone signaling pathways were also detected in the female-restricted group. These results indicate that maternal protein restriction during early developmental periods leads to behavioral deficits and accompanying molecular changes in adult stages.

Free Research Field

分子栄養学

Academic Significance and Societal Importance of the Research Achievements

本研究は、発達期タンパク質栄養制限（対照の半量）により、成熟期の感覚情報フィルター機能が雌性特異的に損なわれ、遺伝子発現変化も導くことを明らかにした。感覚情報フィルター機能障害は、統合失調症のエンドフェノタイプである。本実験では離乳後両群共に約25％タンパク質を含む同一の餌を給餌しており、さらに全期間通じ摂食量は制限していない。しかし、母体栄養に依存する期間においてのみのタンパク質制限だけでも、子宮内発達不全を誘発し、成熟期の精神疾患発症リスクを高める可能性があることを示している。すなわち巷で言われる「小さく生んで大きく育てる」は精神疾患発症の環境要因となる誤った言説であり注意が必要である。