Cold-inducible RNA-binding protein (CIRBP) adjusts clock-gene expression and REM-sleep recovery following sleep deprivation

• DOI: 10.7554/elife.43400
• Publication Date: 2019-02-05T13:00:50Z
• Authors: Marieke MB Hoekstra; Yann Emmenegger; Jeffrey Hubbard; Paul Franken
• Keywords: circadian rhythm; 0301 basic medicine; QH301-705.5; Science; CLOCK Proteins; Gene Expression; Sleep, REM; Gene Knockout Techniques; 03 medical and health sciences; clock genes; Animals; sleep; Biology (General); Mice, Knockout; 2. Zero hunger; 0303 health sciences; Q; R; RNA-Binding Proteins; Animals; CLOCK Proteins/biosynthesis; Gene Expression; Gene Knockout Techniques; Mice, Inbred C57BL; Mice, Knockout; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Sleep Deprivation; Sleep, REM; REM sleep; circadian rhythm; clock genes; cortical temperature; locomotor activity; mouse; neuroscience; sleep; Mice, Inbred C57BL; cortical temperature; Medicine; Sleep Deprivation; REM sleep; locomotor activity; Neuroscience

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.