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Open Access Highly Accessed Research article

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

Ron C Anafi1*, Renata Pellegrino123, Keith R Shockley4, Micah Romer1, Sergio Tufik3 and Allan I Pack1

Author affiliations

1 Division of Sleep Medicine and Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

2 Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

3 Universidade Federal de São Paulo UNIFESP, São Paulo, Brazil

4 Department of Health and Human Services, Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA

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Citation and License

BMC Genomics 2013, 14:362  doi:10.1186/1471-2164-14-362

Published: 30 May 2013

Abstract

Background

Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times.

Results

In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed “sleep specific” changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time.

Conclusion

Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues.

Keywords:
Sleep; Circadian Rhythms; Sleep Deprivation; Unfolded Protein Response; Heart; Lung; Synchronization