A role for cryptochromes in sleep regulation

Jonathan P Wisor; Bruce F O'Hara; Akira Terao; Chris P Selby; Thomas S Kilduff; Aziz Sancar; Dale M Edgar; Paul Franken

doi:10.1186/1471-2202-3-20

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A role for cryptochromes in sleep regulation

Journal article

Open access

Peer reviewed

A role for cryptochromes in sleep regulation

Jonathan P Wisor, Bruce F O'Hara, Akira Terao, Chris P Selby, Thomas S Kilduff, Aziz Sancar, Dale M Edgar and Paul Franken

BMC neuroscience, Vol.3(1), pp.20-20

12/20/2002

DOI: https://doi.org/10.1186/1471-2202-3-20

Handle:

https://hdl.handle.net/2376/110448

PMCID: PMC149230

PMID: 12495442

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https://doi.org/10.1186/1471-2202-3-20View

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Abstract

Protein Kinases - metabolism

Darkness

Protein Kinases - genetics

Rats, Wistar

Male

RNA, Messenger - metabolism

Wakefulness

Trans-Activators - genetics

Sleep - physiology

Nuclear Proteins - genetics

Basic Helix-Loop-Helix Transcription Factors

DNA-Binding Proteins

Delta Rhythm

ARNTL Transcription Factors

Drosophila Proteins

Casein Kinases

Mice, Inbred C57BL

Receptors, G-Protein-Coupled

Rats

Nuclear Proteins - metabolism

Circadian Rhythm - physiology

Transcription Factors - genetics

Nerve Tissue Proteins - genetics

Period Circadian Proteins

Sleep Deprivation - metabolism

Mice, Knockout

Flavoproteins - physiology

Nerve Tissue Proteins - metabolism

Transcription Factors - metabolism

Phenotype

Animals

CLOCK Proteins

Cryptochromes

Trans-Activators - metabolism

Mice

Eye Proteins

Cell Cycle Proteins

Photoreceptor Cells, Invertebrate

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. 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-1epsilon did not change with sleep deprivation. 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.

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Title: A role for cryptochromes in sleep regulation
Creators: Jonathan P Wisor - Dept of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. jwisor@stanford.edu
Bruce F O'Hara
Akira Terao
Chris P Selby
Thomas S Kilduff
Aziz Sancar
Dale M Edgar
Paul Franken
Publication Details: BMC neuroscience, Vol.3(1), pp.20-20
Academic Unit: Biomedical Sciences, Department of
Publisher: England
Grant note: GM31082 / NIGMS NIH HHS R01 MH061755 / NIMH NIH HHS R01 GM031082 / NIGMS NIH HHS HL64243 / NHLBI NIH HHS R37 GM031082 / NIGMS NIH HHS R01MH61755 / NIMH NIH HHS R01HL/MH59658 / NHLBI NIH HHS DA13349 / NIDA NIH HHS HL64148 / NHLBI NIH HHS
Identifiers: 99900547483301842
Language: English
Resource Type: Journal article