Acute sleep fragmentation induces tissue - specific changes in cytokine gene expression and 1 increases serum corticosterone concentration

19 Sleep deprivation induces acute inflammation and increased glucocorticosteroids in 20 vertebrates, but effects from fragmented, or intermittent, sleep are poorly understood. 21 Considering the latter is more representative of sleep apnea in humans, we investigated changes 22 in pro-inflammatory (IL-1β, TNF-α) and anti-inflammatory (TGF-β1) cytokine gene expression 23 in the periphery (liver, spleen, fat, and heart) and brain (hypothalamus, prefrontal cortex, and 24 hippocampus) of a murine model exposed to varying intensities of sleep fragmentation. 25 Additionally, serum corticosterone was assessed. Sleep was disrupted in male C57BL/6J mice 26 using an automated sleep fragmentation chamber that moves a sweeping bar at specified 27 intervals (Lafayette Industries). Mice were exposed to bar sweeps every 20 sec (high sleep 28 fragmentation; HSF), 120 sec (low sleep fragmentation; LSF), or the bar remained stationary 29 (control). Trunk blood and tissue samples were collected after 24 h of SF. We predicted that HSF 30 mice would exhibit increased pro-inflammatory expression, decreased anti-inflammatory 31 expression, and elevated stress hormones in relation to LSF and controls. SF significantly 32 elevated IL-1β gene expression in adipose tissue, heart (HSF only), and hypothalamus (LSF 33 only) relative to controls. SF did not increase TNF-α expression in any of the tissues measured. 34 HSF increased TGF-β1 expression in the hypothalamus and hippocampus relative to other 35 groups. Serum corticosterone concentration was significantly different among groups, with HSF 36 mice exhibiting the highest, LSF intermediate, and controls with the lowest concentration. This 37 indicates that 24 h of SF is a potent inducer of inflammation and stress hormones in the 38 periphery, but leads to upregulation of anti-inflammatory cytokines in the brain. 39