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演題詳細

Symposium

時計遺伝子のその先にあるもの:視交叉上核神経ネットワークがつくる哺乳類の時計機構
Circadian pacemaking beyond clock genes: Neural network-based coherent oscillation and adaptive phasing by the suprachiamatic nucleus

開催日 2014/9/11
時間 9:00 - 11:00
会場 Room F(302)
Chairperson(s) 本間 さと / Sato Honma (北海道大学大学院医学系研究科 時間医学講座 / Department of Physiol Chronomedicine, Hokkaido University Graduate School of Medicine, Japan)
土居 雅夫 / Masao Doi (京都大学大学院薬学研究科医薬創成情報科学専攻システムバイオロジー分野 / Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan)

視交叉上核のバソプレッシン神経結合と時差
Vasopressin-mediated cell-cell communication and jet lag

  • S1-F-1-3
  • 山口 賀章 / Yoshiaki Yamaguchi:1 岡村 均 / Hitoshi Okamura:1 
  • 1:京都大院・薬・システムバイオロジー / Dept Sys-Bio, Kyoto Univ, Kyoto, Japan 

The endogenous circadian clock drives oscillations in physiology and behavior with a period of about 24 hours. We are not usually aware of this system because it is completely synchronized with environmental light-dark cycles, but travelling rapidly across multiple time zones suddenly makes us aware of the desynchrony, causing sleep disturbances and gastrointestinal distress. Repeated jet-lag exposure and rotating shift work increase the risk of lifestyle-related diseases, such as cardiovascular complaints and metabolic insufficiency. Although jet lag is recognized as a chronobiological problem, its specific molecular and cellular mechanisms are poorly understood.
Here, 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). Nevertheless, the behavior of V1aV1bDKO mice was still coupled to the internal clock, which oscillated normally under standard conditions. Response to a light pulse was also normal in V1aV1bDKO mice. 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, which elicits vasopressin signaling as a potential pharmaceutical intervention for management of circadian rhythm misalignment, such as jet lag and shift work.

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