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 journalArticle

33 Citations (Scopus)

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

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anxiety
sleep
clocks
Clocks
Sleep
Anxiety
Pharmacology
wakefulness
mice
circadian rhythms
Wakefulness
Cytoplasmic and Nuclear Receptors
Circadian Rhythm
drugs
disorders
Ligands
proteins
ligands
Molecules
Pharmaceutical Preparations

ASJC Scopus subject areas

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

Cite this

Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour. / Banerjee, Subhashis; Wang, Yongjun; Solt, Laura A.; Griffett, Kristine; Kazantzis, Melissa; Amador, Ariadna; El-Gendy, Bahaa M.; Huitron-Resendiz, Salvador; Roberts, Amanda J.; Shin, Youseung; Kamenecka, Theodore M.; Burris, Thomas P.

In: Nature communications, Vol. 5, 5759, 23.12.2014.

Research output: Contribution to journalArticle

Banerjee, S, Wang, Y, Solt, LA, Griffett, K, Kazantzis, M, Amador, A, El-Gendy, BM, Huitron-Resendiz, S, Roberts, AJ, Shin, Y, Kamenecka, TM & Burris, TP 2014, 'Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour', Nature communications, vol. 5, 5759. https://doi.org/10.1038/ncomms6759
Banerjee, Subhashis ; Wang, Yongjun ; Solt, Laura A. ; Griffett, Kristine ; Kazantzis, Melissa ; Amador, Ariadna ; El-Gendy, Bahaa M. ; Huitron-Resendiz, Salvador ; Roberts, Amanda J. ; Shin, Youseung ; Kamenecka, Theodore M. ; Burris, Thomas P. / Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour. In: Nature communications. 2014 ; Vol. 5.
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