Understanding the role of Ca2+-dependent hyperpolarization pathway in the regulation of sleep homeostasis

• Project/Area Number: 17H06623
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: The University of Tokyo
• Principal Investigator: Shi Shoi 東京大学, 大学院医学系研究科(医学部), 助教 (40803656)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 睡眠恒常性 / 遺伝学 / 睡眠

Outline of Final Research Achievements

This study questions the relationship between sleep homeostasis and the calcium-dependent hyperpolarization pathway. In this study, we clarified the relationship between calcium-dependent hyperpolarization pathway and sleep homeostasis control, and succeeded in identifying Kcnk9 as a novel sleep gene. The results were reported to PNAS, and the invited talk was given at the symposium of the European Sleep Research Society 24th.

Academic Significance and Societal Importance of the Research Achievements

睡眠時間を決める遺伝子を明らかにすることで、その遺伝子もしくは関連遺伝子をターゲットとした安全な睡眠薬の開発が可能です。また睡眠は多くの精神疾患と密接に関わっており、睡眠を制御するメカニズムを解明することは精神疾患に対する新規治療法の開発に繋がる可能性があります。

Research Products

• [Journal Article] Leak potassium channels regulate sleep duration (2018)
  • Author(s): Kensuke Yoshida*, Shoi Shi*, Maki Ukai-Tadenuma, Hiroshi Fujishima, Rei-ichiro Ohno, and Hiroki R. Ueda
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 115 Issue: 40
  • DOI: 10.1073/pnas.1806486115
  • Peer Reviewed / Open Access
• [Journal Article] Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep (2018)
  • Author(s): Niwa Yasutaka、Kanda Genki N.、Yamada Rikuhiro G.、Shi Shoi、Sunagawa Genshiro A.、Ukai-Tadenuma Maki、Fujishima Hiroshi、Matsumoto Naomi、Masumoto Koh-hei、Nagano Mamoru、Kasukawa Takeya、Galloway James、Perrin Dimitri、Shigeyoshi Yasufumi、Ukai Hideki、Kiyonari Hiroshi、Sumiyama Kenta、Ueda Hiroki R.
  • Journal Title: Cell Reports Volume: 24 Issue: 9 Pages: 2231-2247.e7
  • DOI: 10.1016/j.celrep.2018.07.082
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ca2+‐Dependent Hyperpolarization Pathways in Sleep Homeostasis and Mental Disorders (2018)
  • Author(s): Shoi Shi, Hiroki R. Ueda
  • Journal Title: BioEssays Volume: 40 Issue: 1 Pages: 1-15
  • DOI: 10.1002/bies.201700105
  • Peer Reviewed / Open Access
• [Presentation] The impairments of Ca2+-dependent hyperpolarization pathway altered NREM sleep duration in mice (2018)
  • Author(s): 昆一弘, 史蕭逸, 上田泰己
  • Organizer: 18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY
  • Int'l Joint Research
• [Presentation] Newly-identified sleep-related genes: fast and slow Ca2+-dependent hyperpolarization pathway (2018)
  • Author(s): 史蕭逸, 吉田健祐, 上田泰己
  • Organizer: 11th Forum of Neuroscience
  • Int'l Joint Research
• [Presentation] Ca2+-dependent hyperpolarization pathway in sleep homeostasis (2018)
  • Author(s): 史蕭逸
  • Organizer: 24th Congress of the European Sleep Research Society
  • Int'l Joint Research / Invited
• [Presentation] A POTENTIAL PHARMACOLOGICAL TARGET OF INSOMNIA: THE MOLECULES INVOLVED IN THE CA2+-DEPENDENT HYPERPOLARIZATION PATHWAYS PLAY A PIVOTAL ROLE IN THE REGULATION OF SLEEP HOMEOSTASIS (2017)
  • Author(s): Shoi Shi, Hiroki Ueda
  • Organizer: World sleep 2017
  • Int'l Joint Research