ORL1 receptor-mediated down-regulation of mPER2 in the suprachiasmatic nucleus accelerates re-entrainment of the circadian clock following a shift in the environmental light/dark cycle

Kazuko Miyakawa, Ayumi Uchida, Tomomi Shiraki, Koji Teshima, Hiroshi Takeshima, Shigenobu Shibata

    研究成果: Article

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    The circadian pacemaker in the suprachiasmatic nucleus (SCN) generates the near 24-h period of the circadian rhythm and is entrained to the 24-h daily cycle by periodic environmental signals, such as the light/dark cycle (photic signal), and can be modulated by various drugs (non-photic signals). The mechanisms by which non-photic signals modulate the circadian clock are not well understood in mice. In mice, many reportedly non-photic stimuli have little effect on the circadian rhythm in vivo. Herein, we investigated the molecular mechanism in W-212393-induced phase advance using mice. W-212393 caused a significant phase advance of locomotor activity rhythm in mice at subjective day. Injection of W-212393 during subjective day elicited down-regulation of mPER2 protein in the SCN shell region, but not mPer2 mRNA. Administration of W-212393 during subjective day failed to produce phase advance in mPer2-mutant mice as well as in ORL1 receptor deficient mice. Furthermore, we show that such inhibition of mPER2 accelerates re-entrainment of the circadian clock following an abrupt shift in the environmental light/dark cycle, such as occurs with transmeridian flight. The present results suggest that post-translational down-regulation of mPER2 protein in the shell region of mouse SCN may be involved in W-212393-induced non-photic phase advance.

    元の言語English
    ページ(範囲)1055-1064
    ページ数10
    ジャーナルNeuropharmacology
    52
    発行部数3
    DOI
    出版物ステータスPublished - 2007 3

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    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Drug Discovery
    • Pharmacology

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