Molecular mechanism underlying disturbed circadian rhythms in sleep disorder

• Project/Area Number: 24621015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 睡眠科学
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: HIDA Akiko 独立行政法人国立精神・神経医療研究センター, 精神保健研究所・精神生理研究部, 室長 (20333354)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 生物時計 / 睡眠 / 生体リズム

Outline of Final Research Achievements

Circadian clocks regulate daily behavioral and physiological rhythms. These rhythms are generated by a self-sustained clock system. The circadian clock system involves transcription-translation negative feedback loops of multiple clock genes. Circadian rhythm sleep disorders (CRSDs) are defined by persistent or recurrent disturbed sleep-wake cycles and are thought to result from the impairment of the circadian clock system. Clock gene expression was measured in fibroblasts derived from healthy subjects and rhythmic expression was observed in the cells (in vitro rhythm). The period length of in vitro rhythm was correlated with diurnal preference and preferred sleep timing. Evaluating in vitro rhythm may therefore be an appropriate method to assess an individual's circadian clock phenotype. In vitro rhythms were measured in fibroblasts derived from patients with CRSDs and the circadian characteristics of in vitro rhythms were compared to the phenotypes of the patients.

Research Products

• [Journal Article] Screening of Clock Gene Polymorphisms Demonstrates Association of a PER3 Polymorphism with Morningness-Eveningness Preference and Circadian Rhythm Sleep Disorder (2014)
  • Author(s): Hida A, Kitamura S, Katayose Y, Kato M, Ono H, Kadotani H, Uchiyama M, Ebisawa T, Inoue Y, Kamei Y, Okawa M, Takahashi K, Mishima K
  • Journal Title: Scientific Reports Volume: 4(6309) Issue: 1 Pages: 1-6
  • DOI: 10.1038/srep06309
  • NAID: 120007150317
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] In vitro circadian period is associated with circadian/sleep preference. (2013)
  • Author(s): Hida A, 他16名
  • Journal Title: Scientific Reports Volume: 3 Issue: 1 Pages: 2074-2074
  • DOI: 10.1038/srep02074
  • Peer Reviewed
• [Journal Article] 体内時計機能の評価法 (2013)
  • Author(s): 肥田昌子、三島和夫
  • Journal Title: ANTI-AGING MEDICINE Volume: 9(2) Pages: 184-190
• [Journal Article] 生物の体内時計に関する最新知見 (2013)
  • Author(s): 肥田昌子、三島和夫
  • Journal Title: ねむりと医療 Volume: 6(1) Pages: 30-32
• [Journal Article] 睡眠のメカニズムとアレルギー (2013)
  • Author(s): 肥田昌子、三島和夫
  • Journal Title: Progress in Medicine Volume: 33(12) Pages: 2567-2571
• [Journal Article] Rhythmic expression of circadian clock genes in human leukocytes and beard hair follicle cells (2012)
  • Author(s): Watanabe M.
  • Journal Title: Biochem Biophys Res Commun Volume: 425(4) Issue: 4 Pages: 902-7
  • DOI: 10.1016/j.bbrc.2012.08.008
  • Peer Reviewed
• [Journal Article] 肥満と睡眠・生体リズム (2012)
  • Author(s): 肥田昌子, 三島和夫
  • Journal Title: プラクティス Volume: 29 Pages: 275-280
• [Presentation] Association of a PER3 Polymorphism with Morningness–Eveningness Preference and Circadian Rhythm Sleep Disorder (2014)
  • Author(s): Hida A, Kitamura S, Katayose Y, Kato M, Ono H, Kadotani H, Uchiyama M, Ebisawa T, Inoue Y, Kamei Y, Okawa M, Takahashi K, Mishima K
  • Organizer: 第21回日本時間生物学会学術大会
  • Place of Presentation: 福岡 九州大学医学部百年講堂
  • Year and Date: 2014-11-07 – 2014-11-09
• [Presentation] Potential pathogenesis of circadian rhythm sleep disorders (2014)
  • Author(s): Hida A
  • Organizer: Asian Sleep Research Society 2014
  • Place of Presentation: GV Raja Convention Center, Kerala, India
  • Year and Date: 2014-09-22 – 2014-09-24
  • Invited
• [Presentation] 概日リズム睡眠障害の発症機序：末梢時計機能の評価 (2014)
  • Author(s): 肥田昌子, 北村真吾, 中崎恭子, 元村祐貴, 綾部直子, 加藤美恵, 小野浩子, 松井健太郎, 小林美奈, 碓氷章, 井上雄一, 亀井雄一, 三島和夫
  • Organizer: 日本睡眠学会第39回定期学術集会
  • Place of Presentation: 徳島 あわぎんホール
  • Year and Date: 2014-07-03 – 2014-07-04
• [Presentation] Dissection of circadian clock system in humans (2014)
  • Author(s): Hida A
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島 鹿児島大学郡元キャンパス
  • Invited
• [Presentation] Potential pathogenesis of Circadian Rhythm Sleep Disorders (2013)
  • Author(s): Hida A
  • Organizer: Neuro2013
  • Place of Presentation: 京都 国立京都国際会館
  • Invited
• [Presentation] 概日リズム睡眠障害患者の生物時計機能障害 (2013)
  • Author(s): 肥田昌子, 北村真吾, 片寄泰子, 中﨑恭子, 元村祐貴, 大場健太郎, 野崎健太郎, 加藤美恵, 小野浩子, 松井健太郎, 小林美奈, 碓氷章, 井上雄一, 亀井雄一, 三島和夫
  • Organizer: 日本睡眠学会第38回定期学術集会
  • Place of Presentation: 秋田 秋田キャッスルホテル
• [Presentation] 概日リズム睡眠障害患者の体内時計機能障害 (2013)
  • Author(s): 肥田昌子、北村真吾、大澤要介、中崎恭子、元村裕貴、綾部直子、片寄泰子、野崎健太郎、榎本みのり、加藤美恵、小野浩子、亀井雄一、三島和夫
  • Organizer: 第128回日本薬理学会関東部会
  • Place of Presentation: 東京 早稲田大学井深大記念ホール
  • Invited
• [Presentation] In vitro リズムアッセイによる体内時計評価法 (2013)
  • Author(s): 肥田昌子
  • Organizer: 第20回日本時間生物学会学術大会
  • Place of Presentation: 大阪 近畿大学東大阪キャンパス
  • Invited
• [Presentation] Assessment of Individual Circadian Phenotypes Using Biopsy Samples- Application to Circadian Rhythm Sleep Disorder Patients (2012)
  • Author(s): Hida A
  • Organizer: Society for Research on Biological Rhythms 2012
  • Place of Presentation: Beyton Conference Center, Florida, USA
• [Presentation] 生体組織を利用したヒト生物時計機能評価―概日リズム睡眠障害患者への応用― (2012)
  • Author(s): 肥田昌子, 北村真吾, 大澤要介, 榎本みのり, 片寄泰子, 野崎健太郎, 加藤美恵, 守口善也, 亀井雄一, 三島和夫
  • Organizer: 日本睡眠学会第37回定期学術集会
  • Place of Presentation: パシフィコ横浜 神奈川
• [Presentation] 末梢時計リズムは個人の睡眠特性・生物時計機能を反映する (2012)
  • Author(s): 肥田昌子, 北村真吾, 大澤要介, 片寄泰子, 野崎健太郎, 榎本みのり, 有竹清夏, 樋口重和, 加藤美恵, 亀井雄一, 池田正明, 三島和夫
  • Organizer: 第19回日本時間生物学会学術大会
  • Place of Presentation: 北海道大学学術交流会館 北海道
• [Presentation] Effects of E-box and CRE on Per1 expression in SCN and periphery in mice (2012)
  • Author(s): Hida A, Yamazaki S, Mishima K, Johson CH, Tei H.
  • Organizer: 第19回日本時間生物学会学術大会
  • Place of Presentation: 北海道大学学術交流会館 北海道
• [Presentation] Period of fibroblast rhythm predicts individual circadian/sleep properties (2012)
  • Author(s): 肥田 昌子、北村 真吾、片寄 泰子、榎本 みのり、大澤 要介、渡邊 真紀子、野崎 健太郎、有竹 清夏、樋口 重和、加藤 美恵、守口 善也、亀井 雄一、池田 正明、三島 和夫
  • Organizer: Neuroscience2012
  • Place of Presentation: 名古屋国際会議場 愛知
• [Remarks] 国立精神・神経医療研究センター プレスリリース
  • URL: http://www.ncnp.go.jp/press/press_release140909.html
• [Remarks] 国立精神・神経医療研究センター 精神保健研究所 精神生理研究部 ホームページ
  • URL: http://www.ncnp.go.jp/nimh/seiri/
• [Remarks] 国立精神・神経医療研究センター プレスリリース詳細
  • URL: http://www.ncnp.go.jp/press/press_release130705.html
• [Remarks] 国立精神・神経医療研究センター 精神保健研究所 精神生理研究部 研究内容
  • URL: http://labo.sleepmed.jp/research_project.html