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

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-155(KO)) mice and littermate controls (WT). Mice were implanted with biotelemetry units and EEG/EMG biopotentials were recorded continuously for three baseline days. miR-155(KO) 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-155(KO) 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 delta 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-155(KO) mice displayed increased wakefulness and decreased NREM sleep during the dark phase following LPS injection. Additionally, miR-155(KO) 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.