Sleep loss changes microRNA levels in the brain: A possible mechanism for state-dependent translational regulation

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.

Identification of blood microRNAs associated to Parkinsońs disease

“…We are concerned that the present results were obtained from blood, and that these miRNAs may show different expression patterns in brain tissue. Moreover, these differences in miRNA expression may even occur among distinct brain areas (Davis et al, 2007;Kim et al, 2007). The extent of miRNA expression pattern correlation between peripheral blood and different brain structures should be evaluated in future research.…”

“…As an initial step of this study, a PCR array was performed with microRNAs previously reported as potentially associated with both sleep deprivation (Davis et al, 2007) and neurodegenerative disorders (Barbato et al, 2009;Eacker et al, 2009;Kim et al, 2007;Wang et al, 2008). The complete list of the 85 microRNAs used in the PCR array are indicated in Supplementary data Table 2.…”

MicroRNAs in the Hypothalamus

“…In the hypothalamus, miRNA species are both up- and downregulated after sleep deprivation [67]. Intracerebroventricular administration of a miR-132 mimetic (pre-miR-132) decreases the duration of non-rapid eye movement sleep (NREMS), while simultaneously increasing the duration of rapid eye movement sleep (REMS) during the light phase [68].…”

The role of microRNAs (miRNA) in circadian rhythmicity

“…Also, it is possible that moderate-fold change is inherent property of miRNAs, reflecting the role of these regulators in fine tuning of expression. For example, miRNA levels after sleep deprivation in the rat's brain also show modest magnitude of fold-change (1.5-2.5: Davis et al (2007)). …”