Accepted manuscript
5'-Ectonucleotidase-knockout mice lack non-REM sleep responses to sleep deprivation
The European journal of neuroscience, Vol.35(11), pp.1789-1798
06/2012
Handle:
https://hdl.handle.net/2376/111360
PMCID: PMC3370120
PMID: 22540145
Abstract
Adenosine and extracellular adenosine triphosphate (ATP) have multiple physiological central nervous system actions including regulation of cerebral blood flow, inflammation and sleep. However, their exact sleep regulatory mechanisms remain unknown. Extracellular ATP and adenosine diphosphate are converted to adenosine monophosphate (AMP) by the enzyme ectonucleoside triphosphate diphosphohydrolase 1, also known as CD39, and extracellular AMP is in turn converted to adenosine by the 5'-ectonuleotidase enzyme CD73. We investigated the role of CD73 in sleep regulation. Duration of spontaneous non-rapid eye movement sleep (NREMS) was greater in CD73-knockout (KO) mice than in C57BL/6 controls whether determined in our laboratory or by others. After sleep deprivation (SD), NREMS was enhanced in controls but not CD73-KO mice. Interleukin-1 beta (IL1β) enhanced NREMS in both strains, indicating that the CD73-KO mice were capable of sleep responses. Electroencephalographic power spectra during NREMS in the 1.0-2.5 Hz frequency range was significantly enhanced after SD in both CD73-KO and WT mice; the increases were significantly greater in the WT mice than in the CD73-KO mice. Rapid eye movement sleep did not differ between strains in any of the experimental conditions. With the exception of CD73 mRNA, the effects of SD on various adenosine-related mRNAs were small and similar in the two strains. These data suggest that sleep is regulated, in part, by extracellular adenosine derived from the actions of CD73.
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Details
- Title
- 5'-Ectonucleotidase-knockout mice lack non-REM sleep responses to sleep deprivation
- Creators
- Mark R Zielinski - Sleep and Performance Research Center, Programs in Neuroscience, WWAMI Medical Education Program, Washington State University, Spokane, WA 99210-1495, USAPing TaishiJames M ClintonJames M Krueger
- Publication Details
- The European journal of neuroscience, Vol.35(11), pp.1789-1798
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- France
- Grant note
- R01 NS025378 / NINDS NIH HHS R01 NS031453-18 / NINDS NIH HHS NS025378 / NINDS NIH HHS R01 NS031453 / NINDS NIH HHS NS031453 / NINDS NIH HHS R01 NS025378-25 / NINDS NIH HHS
- Identifiers
- 99900547541201842
- Language
- English
- Resource Type
- Accepted manuscript