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分子時計のリズム発振と中枢時計への統合メカニズム

Research Project

Project/Area Number 18019001
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University

Principal Investigator

本間 さと  Hokkaido University, 大学院・医学研究科, 教授 (20142713)

Co-Investigator(Kenkyū-buntansha) 池田 真行  富山大学, 理学部, 准教授 (10288053)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2007: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2006: ¥5,800,000 (Direct Cost: ¥5,800,000)
Keywords生理学 / 神経科学 / 視交叉上核 / 時計遺伝子 / 分子イメージング / 生物発光
Research Abstract

視床下部視交叉上核(SCN)に存在するほ乳類の中枢時計は、網膜からの光情報を受容し、内因性の周期を24時間の明暗サイクルに同調すると共に、SCN外脳内組織や末梢臓器の末梢時計を調節し、全身の時間的統合を行っている。しかし、そのメカニズムは不明である。夜行性齧歯類における行動リズムの季節変動は、これまで、夕日および朝日に同調し、活動の開始と終了を調節するEvening(E)とMorning(M)の二振動体によると考えられてきた。そこで、発光レポータートランスジェニックマウスを用い、SCN細胞のPerl発現リズム位相をSCN内で部位別に測定し、日長と行動リズム位相との相関を解析し、生体が行動や内分泌機能に季節変動を生じる機構について検討した。24時間明暗周期の明期を6〜18時間と変動させたところ、すべての明暗比において、吻側SCNのPerl発現リズムピークは夕方の活動開始位相にphase-lockしており、E振動体の局在が示された。一方、尾側SCNのPerl発現ピークは、測定したすべての明暗比で、朝の活動終了位相にPhase-lockしておりM振動体の局在が示された。尾側SCNのPerlピークのphase-lockingは、明期20および22時間という極端な長日周期でも確認された。明期18時間では吻側SCNのPerl発現が二峰性となり、さらに明期を延長すると吻側、尾側ともに二峰性ピークが観察された。発光イメージングによる細胞リズム解析の結果、すべてのSCN細胞の発光リズムは約24時間であり、二峰性リズムは、ほぼ180度位相が異なり、かつ、左右SCNにほぼ均等に混在する、2種の細胞群によることが分かった。以上の結果、日長によりSCN内で部位時的に遺伝子発現リズム位相を変位させるSCN細胞のダイナミズムが、行動リズムの季節変動を調節していることが分かった。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (34 results)

All 2008 2007 2006

All Journal Article (24 results) (of which Peer Reviewed: 8 results) Presentation (2 results) Book (8 results)

  • [Journal Article] Circadian behavioral rhythms in Cry1/Cry2 double eeficient mice induced by methamphetamine.2008

    • Author(s)
      Honma, S.
    • Journal Title

      J. Biol. Rhythms 22

      Pages: 91-94

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TTX sensitive local circuit is involved in the expression of PK2 and BDNF circadian rhythms in the mouse suprachiasmatic nucleus.2008

    • Author(s)
      Baba, K.
    • Journal Title

      Eur. J. Neurosci. 27

      Pages: 909-916

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Scheduled exposures to a novel environment with a running-wheel differentially accelerate re-entrainment of mice peripheral clocks to new light-dark cycles.2008

    • Author(s)
      Yamanaka, Y.
    • Journal Title

      Genes to Cells (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clock遺伝子と概日リズム形成2008

    • Author(s)
      中村 渉
    • Journal Title

      Clinical Neuroscience 250

      Pages: 1112-1115

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 生体リズムの分子機構2008

    • Author(s)
      吉川朋子
    • Journal Title

      日本臨床 (印刷中)

    • Related Report
      2007 Annual Research Report
  • [Journal Article] ヒト型睡眠の特徴とそのモデル化2008

    • Author(s)
      増渕悟
    • Journal Title

      細胞工学 (印刷中)

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Daily restricted feeding resets the circadian clock in the suprachiasmatic nucleus of CS mice.2007

    • Author(s)
      Abe, H.
    • Journal Title

      Am. J. Physiol. Regul. Integr. Comp. Physiol. 292

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methamphetamine induces circadian oscillation in the brain outside the suprachiamsatic nucleus in rats.2007

    • Author(s)
      Masubuchi, S.
    • Journal Title

      Sleep Biol. Rhythms. 5

      Pages: 132-140

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity.2007

    • Author(s)
      Inagaki, N.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 104

      Pages: 7664-7669

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimization of dosing schedule of daily inhalant dexamethasone to minimize phase-shifting of clock gene expression rhythm in the lungs of the asthma mouse model.2007

    • Author(s)
      Hayasaka, N.
    • Journal Title

      Endocrinology 148

      Pages: 3316-3326

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple regulatory mechanisms for the circadian expression of hepatic Cyp7a.2007

    • Author(s)
      Noshiro, M.
    • Journal Title

      J. Biol. Rhythms 22

      Pages: 299-311

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ラットの眠りをヒトの眠りにーメタンフェタミンモデルを用いた睡眠覚醒リズム制御研究2007

    • Author(s)
      本間さと
    • Journal Title

      週間医学のあゆみ 220

      Pages: 279-284

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 睡眠と生体リズム2007

    • Author(s)
      橋本聡子
    • Journal Title

      日本薬理学会誌 129

      Pages: 400-403

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 中枢時計と末梢時計の統合2007

    • Author(s)
      棚橋祐典
    • Journal Title

      Clinical Neuroscience 250

      Pages: 1105-1108

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity.2007

    • Author(s)
      Inagaki, N.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ラットの眠りをヒトの眠りにーメタンフェタミンモデルを用いた睡眠覚醒リズム制御研究2007

    • Author(s)
      本間さと
    • Journal Title

      週刊医学のあゆみ 220

      Pages: 279-284

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 睡眠と生体リズム2007

    • Author(s)
      橋本聡子
    • Journal Title

      日本薬理学会誌 129(印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of fasting and re-feeding on the expression of Dec1, Per1, and other clock-related genes.2006

    • Author(s)
      Kawamoto, T.
    • Journal Title

      J. Biochem.(Tokyo) 141

      Pages: 401-408

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Daily restricted feeding resets the circadian clock in the suprachiasmatic nucleus of CS mice.2006

    • Author(s)
      Abe, H.
    • Journal Title

      Am. J. Physiol. Regul. Integr. Comp. Physiol. 292

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Repeated exposures to daytime bright light increase nocturnal melatonin rise and keep the circadian phase in young subjects under fixed sleep schedule.2006

    • Author(s)
      Takasu, N.
    • Journal Title

      Am. J. Physiol. Regul. Integr. Comp. Physiol. 291

    • Related Report
      2006 Annual Research Report
  • [Journal Article] New reporter system for Per1 and Bmal1 expressions revealed self-sustained circadian rhythms in peripheral tissues.2006

    • Author(s)
      Nishide, S.
    • Journal Title

      Genes to Cells 11

      Pages: 1173-1182

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of physical exercise on human circadian rhythms.2006

    • Author(s)
      Yamanaka, Y.
    • Journal Title

      Sleep Biol. Rhythms 4

      Pages: 199-206

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 生物時計と神経内分泌のリズム2006

    • Author(s)
      棚橋祐典
    • Journal Title

      脳と神経 58

      Pages: 390-399

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 日内リズムと睡眠2006

    • Author(s)
      遠藤拓郎
    • Journal Title

      THE LUNG perspectives 14

      Pages: 193-196

    • Related Report
      2006 Annual Research Report
  • [Presentation] Clock mechanisms in the suprachiasmatic nucleus coding day length2007

    • Author(s)
      Honma, S.
    • Organizer
      50th Anniversary Meeting of Mexican Physiolo gical Society.
    • Place of Presentation
      Puebra, Mexico
    • Year and Date
      2007-09-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] Clocks regulating behavior rhythms of mammals.2007

    • Author(s)
      Honma, S.
    • Organizer
      Gordon Conference on Chronobiology
    • Place of Presentation
      Aussois, France
    • Year and Date
      2007-05-09
    • Related Report
      2007 Annual Research Report
  • [Book] 時間生物学事典2008

    • Author(s)
      本間 さと
    • Publisher
      朝倉書店(印刷中)
    • Related Report
      2007 Annual Research Report
  • [Book] 睡眠学2008

    • Author(s)
      本間 さと
    • Publisher
      朝倉書店(印刷中)
    • Related Report
      2007 Annual Research Report
  • [Book] New Encyclopedia of Neuroscience2007

    • Author(s)
      Honma, S
    • Publisher
      Elsevier(in press)
    • Related Report
      2006 Annual Research Report
  • [Book] Annual Review 神経2007

    • Author(s)
      本間さと
    • Total Pages
      335
    • Publisher
      中外医学社
    • Related Report
      2006 Annual Research Report
  • [Book] 環境生理学2007

    • Author(s)
      本間さと
    • Total Pages
      446
    • Publisher
      北海道大学出版会
    • Related Report
      2006 Annual Research Report
  • [Book] 時間生物学事典2007

    • Author(s)
      本間さと
    • Publisher
      朝倉書店(印刷中)
    • Related Report
      2006 Annual Research Report
  • [Book] 睡眠学2007

    • Author(s)
      本間さと
    • Publisher
      朝倉書店(印刷中)
    • Related Report
      2006 Annual Research Report
  • [Book] Advances in Network Electrophysiology, Using Multi-Electrode Arrays2006

    • Author(s)
      Honma, S., et al.
    • Total Pages
      478
    • Publisher
      Springer New York
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2018-03-28  

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