2018 Fiscal Year Final Research Report

Brain-gut axis mechanisms formed by mother-pup interactions for the resilience to stress

Research Project

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Project/Area Number	15H02479
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Research Field	Integrative animal science
Research Institution	Azabu University
Principal Investigator	Kikusui Takefumi 麻布大学, 獣医学部, 教授 (90302596)
Co-Investigator(Kenkyū-buntansha)	大野博司国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50233226) 茂木一孝麻布大学, 獣医学部, 准教授 (50347308) 宮内栄治国立研究開発法人理化学研究所, 生命医科学研究センター, 基礎科学特別研究員 (60634706) 森田英利岡山大学, 環境生命科学研究科, 教授 (70257294)
Project Period (FY)	2015-04-01 – 2019-03-31
Keywords	マウス / 母子間 / ストレス / 腸内細菌叢 / 免疫
Outline of Final Research Achievements	In early weaning mice, fear extinction learning was impaired, and BDNFIII mRNA and BDNF protein in the frontal lobe decreased. A negative correlation was also found between them, and it was postulated that the resistance to extinction of fear memory by early weaning involves the attenuation of the BDNF action through the decrease in expression of BDNFIII mRNA in the frontal lobe. Furthermore, it was shown that feces of early weaning mice usually show a different bacterial flora from weaning, and that changes in the bacterial flora are involved in depression-like behavior. In parallel, changes in the intestinal immunoplexus centered, such as Tregs were also confirmed. In addition, experiments to establish the bacterial flora in germ-free mice have shown that the bacterial flora of early weaning mice increased depression behavior and was related to an increase in interindividual distance and a decrease in BDNF in the intracerebral lobe.
Free Research Field	動物行動学
Academic Significance and Societal Importance of the Research Achievements	幼少期の環境が、個体の成長に与える影響、特に不安行動や社会性の障害における影響は、動物に限らずヒト社会でも危急の課題である。今回の研究で、１）幼少期環境は前頭葉の神経栄養因子の発達に特異的なエピジェネティック変化を及ぼすこと、3）並行して腸内細菌叢と免疫系の変化が認められること、４）腸内細菌叢の変化自体が、中枢発達に強い影響を与えること、５）腸内細菌叢を改善することで幼少期ストレスの効果を軽減させる可能性があること、が見いだされた。幼児虐待が増加の一途をたどる現代日本において、その分子生物学的な機序の解明は新たな予防法や治療法に資する成果といえる。