Pathogenesis of developmental disorders based on the physiological coupling between inflammation, serotonin and circadian clock

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16150
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kobe University
• Principal Investigator: Imamura Kiyomichi 神戸大学, 医学研究科, 医学研究員 (20866074)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 概日時計 / 体内時計 / 母体免疫活性化 / 炎症

Outline of Final Research Achievements

Excessive maternal immune activation (MIA) during pregnancy increases the risk of developmental disorders in the offsprings. However, most of underlying mechanisms of it are still obscure. As a disruption of the circadian clock is often observed in the pups with developmental disorders, the relationship between MIA, developmental disorders and the circadian clock was investigated using perinatal mice in which an excessive immune activation was artificially induced. In the present study, we established an experimental condition in which perinatal mice highly express IL-17a, which is known to be a factor that increases the risk of developmental disorders in newborns. The circadian behavioral rhythms in those pups born from MIA mouse tended to show longer period than in the controls.

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

妊娠中の感染症は胎児の発達に深刻な影響を与えうるが、その機構については不明な点が多い。本研究においては、母体感染が引金となる発達障害発症の過程として体内時計（概日時計）の破綻を想定した。マウス母体における免疫反応を活性化させることにより擬似的に感染症を模倣し、出生児における行動リズムを測定したところ、その行動リズム周期が延長する傾向にあることを見出した。本成果は母体感染が発達障害発症を引き起こす過程に迫る上での動物モデルの基盤となりうる。