PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

Hidenori Shirai, Katsutaka Oishi, Takashi Kudo, Shigenobu Shibata, Norio Ishida*

*この研究の対応する著者

研究成果: Article査読

56 被引用数 (Scopus)

抄録

Recent progress at the molecular level has revealed that nuclear receptors play an important role in the generation of mammalian circadian rhythms. To examine whether peroxisome proliferator-activated receptor alpha (PPARα) is involved in the regulation of circadian behavioral rhythms in mammals, we evaluated the locomotor activity of mice administered with the hypolipidemic PPARα ligand, bezafibrate. Circadian locomotor activity was phase-advanced about 3 h in mice given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant darkness did not change the onset of activity in these mice, suggesting that bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate also advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN; the central clock in mammals). The circadian expression of clock genes such as period2, BMAL1, and Rev-erbα was also phase-advanced in various tissues (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase-advanced the activity phase that is delayed in model mice with delayed sleep phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that PPARα is involved in circadian clock control independently of the SCN and that PPARα could be a potent target of drugs to treat circadian rhythm sleep disorders including DSPS.

本文言語English
ページ(範囲)679-682
ページ数4
ジャーナルBiochemical and Biophysical Research Communications
357
3
DOI
出版ステータスPublished - 2007 6月 8

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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