Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour

Subhashis Banerjee, Yongjun Wang, Laura A. Solt, Kristine Griffett, Melissa Kazantzis, Ariadna Amador, Bahaa M. El-Gendy, Salvador Huitron-Resendiz, Amanda J. Roberts, Youseung Shin, Theodore M. Kamenecka, Thomas P. Burris

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the potential to directly modulate the endogenous circadian rhythm and treat diseases associated with clock dysfunction. Here we demonstrate that synthetic ligands targeting a key component of the mammalian clock, the nuclear receptors REV-ERBα and β, regulate sleep architecture and emotional behaviour in mice. REV-ERB agonists induce wakefulness and reduce REM and slow-wave sleep. Interestingly, REV-ERB agonists also reduce anxiety-like behaviour. These data are consistent with increased anxiety-like behaviour of REV-ERBβ-null mice, in which REV-ERB agonists have no effect. These results indicate that pharmacological targeting of REV-ERB may lead to the development of novel therapeutics to treat sleep disorders and anxiety.

Original languageEnglish (US)
Article number5759
JournalNature communications
Volume5
DOIs
StatePublished - Dec 23 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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