miR-155 deletion modulates lipopolysaccharide-induced sleep in female mice.

ABSTRACT

Immune signaling is known to regulate sleep. miR-155 is a microRNA that regulates immune responses. We hypothesized that miR-155 would alter sleep regulation. Thus, we investigated the potential effects of miR-155 deletion on sleep-wake behavior in adult female homozygous miR-155 knockout (miR-155KO) mice and littermate controls (WT). Mice were implanted with biotelemetry units and EEG/EMG biopotentials were recorded continuously for three baseline days. miR-155KO mice had decreased bouts of NREM and REM sleep compared with WT mice, but no differences were observed in the length of sleep bouts or total time spent in sleep-wake states. Locomotor activity and subcutaneous temperature did not differ between WT and miR-155KO mice. Following baseline recordings, mice were sleep-deprived during the first six hours of the rest phase (light phase; ZT 0-6) followed by an 18 h recovery period. There were no differences between groups in sleep rebound (% sleep and NREM δ power) after sleep deprivation. Following recovery from sleep deprivation, mice were challenged with a somnogen (viz., lipopolysaccharide (LPS)) one hour prior to the initiation of the dark (active) phase. Biopotentials were continuously recorded for the following 24 h, and miR-155KO mice displayed increased wakefulness and decreased NREM sleep during the dark phase following LPS injection. Additionally, miR-155KO mice had reduced EEG slow-wave responses (0.5-4 Hz) compared to WT mice. Together, our findings indicate that miR-155 deletion attenuates the somnogenic and EEG delta-enhancing effects of LPS. Abbreviations ANOVA analysis of variance; EEG electroencephalogram; EMG electromyogram; h hour; IL-1 interleukin-1; IL-6 interleukin-6; IP intra-peritoneal; LPS lipopolysaccharide; miR/miRNA microRNA; miR-155KO miR-155 knockout; NREM non-rapid eye movement; REM rapid eye movement; TNF tumor necrosis factor; SWS slow-wave sleep; WT wild-type.