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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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