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

Academic Article
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Overview

related to degree

  • Amador, Ariadna, Ph.D. in Molecular Therapeutics, Scripps Research 2010 - 2016

authors

  • Banerjee, S.
  • Wang, Y.
  • Solt, Laura A.
  • Griffett, K.
  • Kazantzis, M.
  • Amador, Ariadna
  • El-Gendy, B. M.
  • Huitron-Resendiz, S.
  • Roberts, Amanda
  • Shin, Y.
  • Kamenecka, Theodore
  • Burris, Thomas

publication date

  • December 2014

journal

  • Nature Communications  Journal

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-ERB? and ?, 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-ERB?-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.
  • 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.

subject areas

  • ARNTL Transcription Factors
  • Animals
  • Anxiety
  • Behavior, Animal
  • CLOCK Proteins
  • Circadian Clocks
  • Circadian Rhythm
  • Cryptochromes
  • Feedback, Physiological
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Period Circadian Proteins
  • Pyrrolidines
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Reward
  • Signal Transduction
  • Sleep, REM
  • Thiophenes
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Identity

PubMed Central ID

  • PMC4495958

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms6759

PubMed ID

  • 25536025
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Additional Document Info

start page

  • 5759

volume

  • 5

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