MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats

Sleep deprivation was previously reported to alter microRNA (miRNA) levels in the brain; however, the direct effects of any miRNA on sleep have only been described recently. We determined miRNA 138 (miR-138), miRNA let-7b (let-7b), and miRNA 125a-5p (miR-125a) levels in different brain areas at the...

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Bibliographic Details
Published in:Journal of applied physiology (1985) 2012-12, Vol.113 (11), p.1756-1762
Main Authors: Davis, Christopher J, Clinton, James M, Krueger, James M
Format: Article
Language:English
Subjects:
Animals
Brain
Brain - drug effects
Brain - metabolism
Circadian Rhythm
Delta Rhythm - drug effects
Delta Rhythm - genetics
Gene expression
Gene Expression Regulation
Injections, Intraventricular
Male
MicroRNAs - antagonists & inhibitors
MicroRNAs - metabolism
Neuropsychology
Oligonucleotides - administration & dosage
Photoperiod
Rats
Rats, Sprague-Dawley
Ribonucleic acid
RNA
Rodents
Sleep deprivation
Sleep Stages - drug effects
Sleep Stages - genetics
Time Factors
Wakefulness
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Summary:Sleep deprivation was previously reported to alter microRNA (miRNA) levels in the brain; however, the direct effects of any miRNA on sleep have only been described recently. We determined miRNA 138 (miR-138), miRNA let-7b (let-7b), and miRNA 125a-5p (miR-125a) levels in different brain areas at the transitions between light and dark. In addition, we examined the extent to which inhibiting these miRNAs affects sleep and EEG measures. We report that the levels of multiple miRNAs differ at the end of the sleep-dominant light period vs. the end of the wake-dominant dark period in cortical areas, hippocampus, and hypothalamus. For instance, in multiple regions of the cortex, miR-138, let-7b, and miR-125a expression was higher at the end of the dark period compared with the end of the light period. Intracerebroventricular injection of a specific inhibitor (antiMIR) to miR-138 suppressed sleep and nonrapid eye movement sleep (NREMS) EEG delta power. The antiMIR to let-7b did not affect time in state but decreased NREMS EEG delta power, whereas the antiMIR to miR-125a failed to affect sleep until after 3 days and did not affect EEG delta power on any day. We conclude that miRNAs are uniquely expressed at different times and in different structures in the brain and have discrete effects and varied timings on several sleep phenotypes and therefore, likely play a role in the regulation of sleep.
ISSN:8750-7587
1522-1601
DOI:10.1152/japplphysiol.00940.2012