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

doi:10.1038/ncomms6759

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 journal › Article › peer-review

106 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 language	English (US)
Article number	5759
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6759
State	Published - Dec 23 2014
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour",

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.",

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

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doi = "10.1038/ncomms6759",

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AU - Banerjee, Subhashis

AU - Wang, Yongjun

AU - Solt, Laura A.

AU - Griffett, Kristine

AU - Kazantzis, Melissa

AU - Amador, Ariadna

AU - El-Gendy, Bahaa M.

AU - Huitron-Resendiz, Salvador

AU - Roberts, Amanda J.

AU - Shin, Youseung

AU - Kamenecka, Theodore M.

AU - Burris, Thomas P.

PY - 2014/12/23

Y1 - 2014/12/23

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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