Development of biological rhythm adjustment system through eyes for environmental adaptation by integrated analysis of molecule-cell-whole body focused on eye

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H06262
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: Pharmaceutical Sciences and related fields
• Research Institution: Kyushu University
• Principal Investigator: Shigehiro Ohdo 九州大学, 薬学研究院, 教授 (00223884)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 生体リズム / 体内時計 / 時計遺伝子 / 環境応答 / システムバイオロジー

Outline of Final Research Achievements

The SCN（suprachiasmatic nucleus） neurons receive information about light intensity in the environment via direct synaptic connections with the retina, which adapts the phase of SCN oscillator to the photoperiod. The SCN clock then synchronizes overt rhythms in physiology and behavior. Per1 and Per2 transcription is rapidly induced by light in a time-of-day-dependent manner. The responsiveness of Per1 mRNA to light is closely related to behavioral phase delays induced by light. It is well known that not only photic but also nonphotic stimuli can entrain the SCN clock, and Drug A acting on Drug A receptor in retina have been investigated to modulate the circadian rhythm by causing a phase shift in the rhythm in the peripheral or central nervous system. The acute and circadian time-dependent reduction in Per1 and/or Per2 mRNA in SCN and liver by Drug A receptor agonist strongly correlated with phase resetting in response to the drug.

Free Research Field

薬学およびその関連分野

Academic Significance and Societal Importance of the Research Achievements

本研究により、Drug A はDrug A 受容体を介し、時計中枢の時計遺伝子と行動のリズムを制御できた。また、体内時計の同調因子として最も強力とされる光に対して、Drug A 受容体は重要な働きを示した。Drug A 受容体を作用点とするDrug A は、中枢のみならず末梢の時計遺伝子発現に影響を及ぼすことから、Drug A 点眼により生体リズムの位相を操作できる。Drug A 点眼治療を行っている患者は、多く存在しており、Drug A 点眼により体内時計が変化していることが想定される。Drug A 点眼は、社会の多様化により乱れた体内時計を調整し、健康増進に貢献できる可能性がある。