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2013 Fiscal Year Final Research Report

An elucidation of hierarchy of a biological clock and a rhythm adjustment drug by generating a novel clock function-deficient mouse

Research Project

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Project/Area Number 23590107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto University

Principal Investigator

YAMAGUCHI Yoshiaki  京都大学, 薬学研究科(研究院), 助教 (30467427)

Project Period (FY) 2011 – 2013
Keywords視交叉上核 / 概日時計 / 時計遺伝子 / 時差 / バソプレッシン / 遺伝子改変マウス
Research Abstract

The endogenous circadian clock drives oscillations in physiology and behavior with a period of about 24 hours. When travelling rapidly across multiple time zones (jet lag), we become aware of the desynchrony between our internal clock and external light-dark cycle. Although jet lag is recognized as a chronobiological problem, its specific molecular and cellular mechanisms are poorly understood.
In this study, we show that circadian rhythms of locomotor activity, clock gene expression, and body temperature rapidly re-entrained to phase-shifted light-dark cycles in mice genetically deficient in V1a and V1b receptors (V1aV1bDKO). Real-time imaging of cellular rhythms in the suprachiasmatic nucleus (SCN) slices suggested that interneuronal communication mediated by V1a and V1b confers on the SCN an intrinsic resistance to external rhythm perturbation. Pharmacological blockade of V1a and V1b in the SCN of wild-type mice accelerated the speed of recovery from jet lag.

  • Research Products

    (19 results)

All 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (5 results) Book (4 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Mice Genetically Deficient in Vasopressin V1a and V1b Receptors Are Resistant to Jet Lag2013

    • Author(s)
      Yamaguchi Y, Suzuki T, Mizoro Y, Kori H, Okada K, Chen Y, Fustin JM, Yamazaki F, Mizuguchi N, Zhang J, Dong X, Tsujimoto G, Okuno Y, Doi M, Okamura H
    • Journal Title

      Science

      Volume: 342 Pages: 85-90

    • DOI

      10.1126/science.1238599

    • Peer Reviewed
  • [Journal Article] RNA methylation-dependent RNA processing modulates the speed of the circadian clock2013

    • Author(s)
      Fustin JM, Doi M, Yamaguchi Y, Nishimura S, Yoshida M, Isagawa T, Morioka MS, Kakeya H, Manabe I, Okamura H
    • Journal Title

      Cell

      Volume: 155 Pages: 793-806

    • DOI

      10.1016/j.cell.2013.10.026

    • Peer Reviewed
  • [Journal Article] 【ライフサイエンス新着論文レビューFIRST AUTHOR'S】バソプレッシン受容体V1aおよびV1bを欠損したマウスは時差症状を示さない2013

    • Author(s)
      山口賀章, 鈴木暢, 岡村均
    • URL

      http://first.lifesciencedb.jp/archives/7777

    • Peer Reviewed
  • [Journal Article] 視交叉上核2013

    • Author(s)
      山口賀章, 岡村均
    • Journal Title

      脳科学辞典

    • URL

      http://bsd.neuroinf.jp/w/index.php?title=%E8%A6%96%E4%BA%A4%E5%8F%89%E4%B8%8A%E6%A0%B8&oldid=21150

  • [Journal Article] Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus2011

    • Author(s)
      Doi M, Ishida A, Miyake A, Sato M, Komatsu R, Yamazaki F, Kimura I, Tsuchiya S, Kori H, Seo K, Yamaguchi Y, Matsuo M, Fustin JM, Tanaka R, Santo Y, Yamada H, Takahashi Y, Araki M, Nakao K, Aizawa S, Kobayashi M, Obrietan K, Tsujimoto G, Okamura H
    • Journal Title

      Nature communications

      Volume: 2 Pages: 327

    • DOI

      10.1038/ncomms1316

    • Peer Reviewed
  • [Journal Article] Accurate Determination of S-Phase Fraction in Proliferative Cells by Dual Fluorescence and Peroxidase Immunohistochemistry with 5-Bromo-2'-Deoxyuridine (BrdU) and Ki67 Antibodies2011

    • Author(s)
      Tanaka R, Tainaka M, Ota T, Mizuguchi N, Kato H, Urabe S, Chen Y, Fustin JM, Yamaguchi Y, Doi M, Hamada S, Okamura H
    • Journal Title

      J Histochem Cytochem

      Volume: 59 Pages: 791-798

    • DOI

      10.1369/0022155411411090

    • Peer Reviewed
  • [Journal Article] Transportin 1 in the mouse brain : Appearance in regions of neurogenesis, cerebrospinal fluid production/sensing, and circadian clock2011

    • Author(s)
      Sato M, Mizoro Y, Atobe Y, Fujimoto Y, Yamaguchi Y, Fustin JM, Doi M, Okamura H
    • Journal Title

      J Comp Neurol

      Volume: 519 Pages: 1770-1780

    • DOI

      10.1002/cne.22600

    • Peer Reviewed
  • [Journal Article] Hypertension due to loss of clock : novel insight from the molecular analysis of cry1/cry2-deleted mice2011

    • Author(s)
      Okamura H, Doi M, Yamaguchi Y, Fustin JM
    • Journal Title

      Current hypertension reports

      Volume: 13 Pages: 103-108

    • DOI

      10.1007/s11906-011-0181-3

    • Peer Reviewed
  • [Presentation] 時差消失マウスを用いた時差の分子機構の解明2013

    • Author(s)
      山口賀章、岡村均
    • Organizer
      第20回日本時間生物学会学術大会
    • Place of Presentation
      近畿大学、シンポジウム
    • Year and Date
      2013-11-09
  • [Presentation] 視交叉上核の外的撹乱因子に対する抵抗性と時差2013

    • Author(s)
      山口賀章、溝曽路祥孝、郡宏、鈴木暢、岡村均
    • Organizer
      第20回日本時間生物学会学術大会
    • Place of Presentation
      近畿大学、ポスター
    • Year and Date
      2013-11-09
  • [Presentation] Molecular, cellular, and physiological dynamics under experimental jet lag2013

    • Author(s)
      Yoshiaki Yamaguchi and Hitoshi Okamura
    • Organizer
      XIII Congress of the European Biological Rhythms Society、Munich
    • Place of Presentation
      Germany、ポスター
    • Year and Date
      2013-08-19
  • [Presentation] 急性概日リズム睡眠障害である時差症候群の分子機構2013

    • Author(s)
      山口賀章、岡村均
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      国立京都国際会館、シンポジウム
    • Year and Date
      2013-06-20
  • [Presentation] 時差モデルの分子解析2012

    • Author(s)
      山口賀章、岡村均
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場、シンポジウム
    • Year and Date
      2012-09-21
  • [Book] 【最新臨床睡眠学-睡眠障害の基礎と臨床-】神経インパルスからホルモンへの時間変換機構2013

    • Author(s)
      山口賀章, 岡村均
    • Total Pages
      71, 705-710
    • Publisher
      日本臨床
  • [Book] 【代謝内分泌神経ネットワーク】生物時計と臓器ネットワーク:時差の体内機構2013

    • Author(s)
      山口賀章, 岡村均
    • Total Pages
      28, 29-34
    • Publisher
      BIO Clinica
  • [Book] 【ナノバイオ技術と最新創薬応用研究】(第1章)ナノバイオ創薬に向けたターゲットの探索と構造解析概日リズムの分子機構と創薬2012

    • Author(s)
      山口賀章, 岡村均
    • Total Pages
      47-51
    • Publisher
      遺伝子医学MOOK
  • [Book] 【睡眠と生活習慣病-基礎・臨床研究の最新知見-】時計遺伝子・概日リズム概日リズム発振の遺伝子機構2012

    • Author(s)
      山口賀章, 岡村均
    • Total Pages
      70, 1115-1120
    • Publisher
      日本臨床
  • [Remarks]

    • URL

      http://www.pharm.kyoto-u.ac.jp/system-biology/

  • [Patent(Industrial Property Rights)] 概日リズム調整2012

    • Inventor(s)
      岡村均、山口賀章、辻本豪三
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2012-120083
    • Filing Date
      2012-05-25

URL: 

Published: 2015-07-16  

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