A role for cryptochromes in sleep regulation

Jonathan P Wisor¹ , Bruce F O'Hara² , Akira Terao³ , Chris P Selby⁴ , Thomas S Kilduff³ , Aziz Sancar⁴ , Dale M Edgar¹ and Paul Franken²

¹Dept. of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

²Dept. of Biological Sciences, Stanford University, Stanford, CA, USA

³Molecular Neurobiology Laboratory, SRI International, Menlo Park, CA, USA

⁴Dept. of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC, USA

author email corresponding author email

BMC Neuroscience 2002, 3:20doi:10.1186/1471-2202-3-20


Published:	20 December 2002

Abstract

Background

The cryptochrome 1 and 2 genes (cry1 and cry2) are necessary for the generation of circadian rhythms, as mice lacking both of these genes (cry1,2^-/-) lack circadian rhythms. We studied sleep in cry1,2^-/-mice under baseline conditions as well as under conditions of constant darkness and enforced wakefulness to determine whether cryptochromes influence sleep regulatory processes.

Results

Under all three conditions, cry1,2^-/-mice exhibit the hallmarks of high non-REM sleep (NREMS) drive (i.e., increases in NREMS time, NREMS consolidation, and EEG delta power during NREMS). This unexpected phenotype was associated with elevated brain mRNA levels of period 1 and 2 (per1,2), and albumin d-binding protein (dbp), which are known to be transcriptionally inhibited by CRY1,2. To further examine the relationship between circadian genes and sleep homeostasis, we examined wild type mice and rats following sleep deprivation and found increased levels of per1,2 mRNA and decreased levels of dbp mRNA specifically in the cerebral cortex; these changes subsided with recovery sleep. The expression of per3, cry1,2, clock, npas2, bmal1, and casein-kinase-1ε did not change with sleep deprivation.

Conclusions

These results indicate that mice lacking cryptochromes are not simply a genetic model of circadian arrhythmicity in rodents and functionally implicate cryptochromes in the homeostatic regulation of sleep.