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REM sleep: unique associations with corticosterone regulation, apoptotic pathways and behavior in chronic stress in mice

Nollet, Mathieu, Hicks, Harriet, McCarthy, Andrew P., Wu, Huihai, Moller-Levet, Carla S., Laing, Emma E., Malki, Karim, Lawless, Nathan, Wafford, Keith A., Dijk, Derk-Jan and Winsky-Sommerer, Raphaelle (2019) REM sleep: unique associations with corticosterone regulation, apoptotic pathways and behavior in chronic stress in mice Proceedings of the National Academy of Sciences, 116 (7). pp. 2733-2742.

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One of sleep’s putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience, however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine and behavioral variables, as well as the brain and blood transcriptome in mice exposed to nine weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypical variables revealed that rapid-eye-movement sleep (REMS), corticosterone regulation and coat state were most responsive to UCMS. REMS theta oscillations were enhanced whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus and blood were associated with inflammatory and immune responses. A machine learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters which were enriched in 193 pathways, including some involved in stem cells, immune response, apoptosis and survival. Only 3 pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS and anhedonia shared pathways involved in oxidative stress, cell proliferation and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Hicks, Harriet
McCarthy, Andrew P.
Moller-Levet, Carla
Laing, Emma
Malki, Karim
Lawless, Nathan
Wafford, Keith A.
Date : 12 February 2019
DOI : 10.1073/pnas.1816456116
Copyright Disclaimer : Copyright © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Uncontrolled Keywords : Depression; Anhedonia; EEG theta power; Machine learning; Transcriptome
Related URLs :
Additional Information : This article contains supporting information online at 1073/pnas.1816456116/-/DCSupplemental.
Depositing User : Clive Harris
Date Deposited : 18 Jan 2019 12:33
Last Modified : 19 Mar 2019 10:45

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