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

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1055-1064
    Number of pages10
    JournalNeuropharmacology
    Volume52
    Issue number3
    DOIs
    Publication statusPublished - 2007 Mar

    Fingerprint

    Circadian Clocks
    Suprachiasmatic Nucleus
    Photoperiod
    Down-Regulation
    Circadian Rhythm
    Locomotion
    nociceptin receptor
    Proteins
    2-(3-(1-(acenaphthen-1-yl)piperidin-4-yl)-2,3-dihydro-2-oxobenzimidazol-1-yl)-N-methylacetamide
    Messenger RNA
    Injections
    Pharmaceutical Preparations

    Keywords

    • Circadian rhythms
    • Non-photic
    • ORL1 receptor
    • PER2
    • Re-entrainment
    • Suprachiasmatic nucleus

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Drug Discovery
    • Pharmacology

    Cite this

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

    In: Neuropharmacology, Vol. 52, No. 3, 03.2007, p. 1055-1064.

    Research output: Contribution to journalArticle

    @article{0090b5754e444e25bc99ac9d6b7af42f,
    title = "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",
    abstract = "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.",
    keywords = "Circadian rhythms, Non-photic, ORL1 receptor, PER2, Re-entrainment, Suprachiasmatic nucleus",
    author = "Kazuko Miyakawa and Ayumi Uchida and Tomomi Shiraki and Koji Teshima and Hiroshi Takeshima and Shigenobu Shibata",
    year = "2007",
    month = "3",
    doi = "10.1016/j.neuropharm.2006.11.003",
    language = "English",
    volume = "52",
    pages = "1055--1064",
    journal = "Neuropharmacology",
    issn = "0028-3908",
    publisher = "Elsevier Limited",
    number = "3",

    }

    TY - JOUR

    T1 - 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

    AU - Miyakawa, Kazuko

    AU - Uchida, Ayumi

    AU - Shiraki, Tomomi

    AU - Teshima, Koji

    AU - Takeshima, Hiroshi

    AU - Shibata, Shigenobu

    PY - 2007/3

    Y1 - 2007/3

    N2 - 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.

    AB - 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.

    KW - Circadian rhythms

    KW - Non-photic

    KW - ORL1 receptor

    KW - PER2

    KW - Re-entrainment

    KW - Suprachiasmatic nucleus

    UR - http://www.scopus.com/inward/record.url?scp=33846868406&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=33846868406&partnerID=8YFLogxK

    U2 - 10.1016/j.neuropharm.2006.11.003

    DO - 10.1016/j.neuropharm.2006.11.003

    M3 - Article

    C2 - 17196226

    AN - SCOPUS:33846868406

    VL - 52

    SP - 1055

    EP - 1064

    JO - Neuropharmacology

    JF - Neuropharmacology

    SN - 0028-3908

    IS - 3

    ER -