Screening for natural compounds modulating circadian rhythm

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17797
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science; Food science
• Research Institution: Nagoya University
• Principal Investigator: Nakane Yusuke 名古屋大学, 生命農学研究科(WPI), 特任講師 (40792023)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 概日リズム / ケミカルスクリーニング / 食品関連化合物 / 天然化合物 / 時計遺伝子

Outline of Final Research Achievements

Drug discovery of compounds modulating the circadian rhythm could be a potential application for medical treatments, animal productivity etc. because the circadian rhythm is deeply associated with phenomena such as sleep disorders and seasonal reproduction in animals. We found ferulic acid that lengthened the circadian period out of more than 600 food-related compounds with an experiment that we can monitor the expression of a clock gene that drives circadian rhythms. It was also found that this compound could lengthen the sleep-wake cycle in mice. However, administration of this compound to mice did not show a reduction of days to entrain to the new shift under a light/dark cycle that mimics a shift-style work. The administration to ClockΔ19 mice partially ameliorated the manic-like behavior that this clock mutant mice indicate, but didn’t show the improvement of anxiety-like behaviors.

Free Research Field

動物統合生理学

Academic Significance and Societal Importance of the Research Achievements

普段我々が口にする食品に豊富に含まれる天然化合物は安全性が比較的高く日常摂取が可能である。この中から概日リズム調節化合物を新規に見出すことができれば、概日リズムの撹乱に対する日常的な予防効果が期待できる。培養細胞を用いた実験を通して発見した当該化合物は、マウスの睡眠覚醒リズムにも影響を与えることがわかった。種々の疾患モデル動物では当該化合物の明確な症状改善効果は見られなかったが、今後当該化合物の作用機序を明らかにすることは、どの疾患に有効かを理解するための重要な知見となる。また見出された作用機序が新規であった場合、従来とは異なる新規な概日リズム発振機構を発見できるため学術的な展開も期待できる。