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.
Highlights
The sleep-wake distribution is coordinated by the interaction of a circadian and a sleep homeostatic process (Daan et al, 1984)
PER:CRY complexes inhibit CLOCK/NPAS2:ARNTL-transcriptional activity thereby preventing their own transcription. Clock components such as the transcriptional repressor NR1D1 regulate the transcription of Arntl, ensuring together with other transcriptional feedback loops a period of ca. 24 hr (Lowrey and Takahashi, 2011). While this clock-gene circuitry is functionally expressed in almost each cell of the body, peripherally generated circadian rhythms are coordinated by a central pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus, assuring proper circadian time-keeping at the organismal level (Hastings et al, 2018)
Sleep deprivation [between Zeitgeber Time (ZT)0–6] led to an almost uninterrupted period of 6 hr waking, during which locomotor activity and cortical temperature reached values comparable to those reached during bouts of spontaneous wakefulness under undisturbed baseline conditions (i.e. ZT12-18)
Summary
The sleep-wake distribution is coordinated by the interaction of a circadian and a sleep homeostatic process (Daan et al, 1984). The molecular basis of the circadian process consists of clock genes that interact through transcriptional/translational feedback loops. Clock components such as the transcriptional repressor NR1D1 regulate the transcription of Arntl, ensuring together with other transcriptional feedback loops a period of ca. 24 hr (Lowrey and Takahashi, 2011) While this clock-gene circuitry is functionally expressed in almost each cell of the body, peripherally generated circadian rhythms are coordinated by a central pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus, assuring proper circadian time-keeping at the organismal level (Hastings et al, 2018)
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