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Published on: June 19, 2019
Sleep loss changes microRNA levels in the brain: a possible mechanism for state-dependent translational regulation
Christopher J Davis1, Stewart G Bohnet, Joseph M Meyerson
1Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology and Program in Neuroscience, Washington State University, Pullman, WA 99164-6520, United States. cjdavis@vetmed.wsu.edu
Abstract:
MicroRNAs (miRNAs) are small ( approximately 22 nucleotides) non-coding RNA strands that base pair with mRNA to degrade it or inhibit its translation. Because sleep and sleep loss induce changes in many mRNA species, we hypothesized that sleep loss would also affect miRNA levels in the brain. Rats were sleep-deprived for 8h then decapitated; hippocampus, prefrontal and somatosensory cortices and hypothalamus tissues were harvested and frozen in liquid nitrogen. miRNA was extracted and then characterized using microarrays. Several let-7 miRNA microarray results using hippocampus and prefrontal cortex samples were verified by PCR. From the array data it was determined that about 50 miRNA species were affected by sleep loss. For example, in the hippocampus of sleep-deprived rats, miRNA expression increased compared to cage control samples. In contrast, the majority of miRNA species in the somatosensory and prefrontal cortices decreased, while in the hypothalamus miRNA species were both up- and down-regulated after sleep deprivation. The number of miRNA species affected by sleep loss, their differential expression in separate brain structures and their predicted targets suggest that they have a role in site-specific sleep mechanisms. Current results are, to our knowledge, the first demonstration of the homeostatic process, sleep, altering brain miRNA levels.
Insights
Sleep deprivation alters microRNA (miRNA) levels in specific brain regions of rats. These findings reveal a novel link between sleep regulation and miRNA activity in the brain.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are small non-coding RNA molecules regulating gene expression by targeting messenger RNA (mRNA).
- Sleep and sleep deprivation are known to influence the expression of numerous mRNA species in the brain.
- The impact of sleep loss on miRNA levels within the brain remained largely unexplored.
Purpose of the Study:
- To investigate the hypothesis that sleep loss affects miRNA levels in the rat brain.
- To identify specific miRNA species and brain regions impacted by sleep deprivation.
- To explore the potential role of these miRNAs in sleep regulation mechanisms.
Main Methods:
- Rats were subjected to 8 hours of sleep deprivation.
- Specific brain tissues (hippocampus, prefrontal cortex, somatosensory cortex, hypothalamus) were harvested.
- MicroRNA levels were analyzed using microarrays, with select results validated by PCR.
Main Results:
- Approximately 50 different miRNA species were found to be affected by sleep loss.
- Differential regulation of miRNAs was observed across brain regions: increased in the hippocampus, decreased in the somatosensory and prefrontal cortices, and mixed in the hypothalamus.
- Validation confirmed significant changes in specific let-7 miRNA levels in the hippocampus and prefrontal cortex.
Conclusions:
- Sleep deprivation significantly alters the expression profile of miRNAs in distinct rat brain structures.
- The identified miRNAs and their differential expression patterns suggest a role in site-specific sleep regulatory mechanisms.
- This study provides the first evidence that the homeostatic process of sleep influences brain miRNA levels.
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