Cold Inducible RNA-binding protein (CIRBP) adjusts clock-gene expression and REM-sleep recovery after sleep deprivation
Abstract
Sleep depriving mice affects clock-gene expression, suggesting that these genes contribute to sleep homeostasis. The mechanisms linking extended wakefulness to clock-gene expression are, however, not well understood. We propose CIRBP to play a role because its rhythmic expression is i) sleep-wake driven and ii) necessary for high-amplitude clock-gene expression in vitro. We therefore expect Cirbp knock-out (KO) mice to exhibit attenuated sleep-deprivation induced changes in clock-gene expression, and consequently to differ in their sleep homeostatic regulation. Lack of CIRBP indeed blunted the sleep-deprivation incurred changes in cortical expression of Nr1d1 whereas it amplified the changes in Per2 and Clock. Concerning sleep homeostasis, KO mice accrued only half the extra REM sleep wild-type (WT) littermates obtained during recovery. Unexpectedly, KO mice were more active during lights-off which was accompanied with faster theta oscillations compared to WT mice. Thus, CIRBP adjusts cortical clock-gene expression after sleep deprivation and expedites REM-sleep recovery.
Data availability
Source data files underlying all figures have been provided.
Article and author information
Author details
Funding
Swiss National Science Foundation (146694)
- Marieke MB Hoekstra
Etat de Vaud
- Marieke MB Hoekstra
- Yann Emmenegger
- Jeffrey Hubbard
- Paul Franken
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Louis J Ptáček, University of California, San Francisco, United States
Ethics
Animal experimentation: All experiments were approved by the Ethical Committee of the State of Vaud Veterinary Office Switzerland under license VD2743 and 3201.
Version history
- Received: November 6, 2018
- Accepted: February 4, 2019
- Accepted Manuscript published: February 5, 2019 (version 1)
- Version of Record published: February 18, 2019 (version 2)
- Version of Record updated: February 25, 2019 (version 3)
Copyright
© 2019, Hoekstra et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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