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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-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.

SUBMITTER: Banerjee S

PROVIDER: S-EPMC4495958 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Banerjee Subhashis S Wang Yongjun Y Solt Laura A LA Griffett Kristine K Kazantzis Melissa M Amador Ariadna A El-Gendy Bahaa M BM Huitron-Resendiz Salvador S Roberts Amanda J AJ Shin Youseung Y Kamenecka Theodore M TM Burris Thomas P TP

Nature communications 20141223

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-ER ...[more]

PMID: 25536025

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Project description:BackgroundSuicide is the second leading cause of death in adolescents. Sleep disturbances could alter inhibitory processes and contribute to dangerous behaviors in this critical developmental period. Adolescents in suicidal crisis have been shown to have lighter sleep compared to healthy controls. Additionally, suicidal adolescents have lower neural resources mobilized by emotionally charged inhibition processing. The present exploratory study aimed to determine how sleep architecture in suicidal adolescents may relate to inhibition processing in response to emotional stimuli.MethodsTen adolescents between 12 and 17 years of age with a diagnosis of major depressive disorder and who attempted suicide were recruited while hospitalized for a suicidal crisis in a psychiatric inpatient unit. Event-related potentials (ERPs) were recorded prior to bedtime during a Go/NoGo task involving pictures of sad, happy, and neutral faces. Polysomnography was then recorded throughout the night. Pearson correlations were conducted to investigate how inhibition performance and ERP parameters reflecting inhibition processing (i.e., P3d and N2d derived from difference waveform calculated as NoGo minus Go trials) relate to sleep architecture.ResultsPoorer inhibition accuracy in response to emotional stimuli was significantly correlated with shorter REM sleep latency, higher REM sleep, and more frequent nocturnal awakenings. The P3d in response to sad faces was negatively correlated with NREM2 sleep and positively correlated with NREM3 sleep. No such association with the P3d was found for happy or neutral stimuli. There were no significant correlations for the N2d.ConclusionAltered sleep in adolescents with depression who are in a suicidal crisisis associated with behavioral inhibition difficulties and fewer neural resources mobilized by inhibitory processes in emotionally charged contexts. This highlights the importance of addressing sleep disturbances while managing suicidal crises in adolescents.

Dataset Information

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

Publications

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

Similar Datasets

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