Functional assessment of the circadian clock of patients with neurodegenerative disorders based on clock gene expression

• Project/Area Number: 16K15562
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Yamaguchi University
• Principal Investigator: Akashi Makoto 山口大学, 時間学研究所, 教授 (30398119)
• Research Collaborator: TATSUMOTO Muneto ; YAMAGUCHI Ai ; MATSUMURA Ritsuko ; SUMINO Junko
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 概日時計 / 時計遺伝子 / 認知症 / 行動概日リズム

Outline of Final Research Achievements

Extensive studies based on animal experiments have demonstrated that aging results in circadian dysfunction. Here, we performed functional assessment of the clock machinery based on circadian clock gene expression in elderly patients aged 83 to 94 with severe dementia who showed abnormal circadian behavior. Specifically, to investigate whether or not the systemic pathway from the circadian input to peripheral clocks via the suprachiasmatic nucleus (SCN) functioned normally, the circadian phase in peripheral clock gene expression rhythms was evaluated using plucked hair tissues. Unexpectedly, the phase in all volunteer patients was within a range similar to that of healthy subjects, indicating that the systemic circadian pathway is robust against aging and dementia. Taken together, these findings indicate that the circadian pathway from external inputs to peripheral clocks via the SCN may function normally, even in the old-old with severe dementia.

Research Products

• [Journal Article] A simple method using ex vivo culture of hair follicle tissue to investigate intrinsic circadian characteristics in humans (2017)
  • Author(s): Yamaguchi Ai、Matsumura Ritsuko、Matsuzaki Takashi、Nakamura Wataru、Node Koichi、Akashi Makoto
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 6824-6824
  • DOI: 10.1038/s41598-017-07268-8
  • Peer Reviewed / Open Access
• [Journal Article] Estimation methods for human circadian phase by use of peripheral tissues (2016)
  • Author(s): Matsumura. R., Node. K., and Akashi. M.
  • Journal Title: Hypertension Research Volume: 39 Issue: 9 Pages: 623-627
  • DOI: 10.1038/hr.2016.68
  • Peer Reviewed
• [Presentation] 概日時計を研究する意義 (2016)
  • Author(s): 明石 真
  • Organizer: 第３８回日本臨床栄養学会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-10-07
  • Invited
• [Book] 生体の科学 (2016)
  • Author(s): 明石 真
  • Publisher: 医学書院
• [Book] 実験医学増刊号 (2016)
  • Author(s): 明石 真
  • Publisher: 羊土社