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Published on: September 22, 2023
MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats
Christopher J Davis1, James M Clinton, James M Krueger
1WWAMI Medical Education Program, Washington State University, Spokane, Washington 99210, USA. cjdavis@wsu.edu
Abstract:
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.
Insights
MicroRNAs (miRNAs) show distinct brain expression patterns correlating with sleep-wake cycles. Inhibiting specific miRNAs, like miR-138, directly impacts sleep duration and intensity, revealing their regulatory role.
Area of Science:
- Neuroscience
- Molecular Biology
- Sleep Research
Background:
- Sleep deprivation is known to alter microRNA (miRNA) levels in the brain.
- Recent studies have begun to elucidate the direct impact of specific miRNAs on sleep regulation.
Purpose of the Study:
- To investigate the expression patterns of miR-138, let-7b, and miR-125a in different brain regions during light-dark cycle transitions.
- To determine the effects of inhibiting these specific miRNAs on sleep architecture and electroencephalogram (EEG) measures.
Main Methods:
- Quantification of miR-138, let-7b, and miR-125a levels in cortical areas, hippocampus, and hypothalamus at the end of light and dark periods.
- Intracerebroventricular administration of miRNA-specific inhibitors (antiMIRs) to assess impacts on sleep and NREMS EEG delta power.
Main Results:
- Multiple miRNAs exhibited differential expression between the end of the light (sleep) and dark (wake) periods across brain regions.
- Inhibition of miR-138 significantly reduced total sleep time and NREMS EEG delta power.
- let-7b inhibition decreased NREMS EEG delta power, while miR-125a inhibition showed delayed effects on sleep and no impact on EEG delta power.
Conclusions:
- miRNAs are differentially expressed in brain structures and at specific times, suggesting a role in circadian regulation.
- Specific miRNAs, particularly miR-138, play a direct and time-sensitive role in regulating sleep quantity and quality, including NREMS intensity.
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