Microglia Are Necessary to Regulate Sleep after an Immune Challenge

SIMPLE SUMMARY: Microglia are cells in the brain that mediate inflammation, but little is known about the role of microglia in sleep following an inflammatory challenge. We hypothesized that mice with depleted microglia would sleep less following an injection of a particle that causes inflammation in the body and brain. Brains were collected, the shape and complexity of microglia were measured, and biological data were collected to determine how long the mice slept. Mice fed PLX5622 (PLX), a compound that depletes microglia, had an immediate increase in sleep that resolved by week 2. After the first injection to cause inflammation, mice with depleted microglia slept more than control mice that had normal microglia. The PLX diet was switched to a standard mouse diet and microglia returned to the brain. While microglia were returning, there were no changes in sleep. However, following a second injection to cause inflammation, mice that had new microglia slept the same as control mice during the dark period, but had longer episodes of sleep during the light period. Comparing sleep after the first and second inflammation injection, control mice had different sleep patterns but no change in total time spent sleeping. Mice with new microglia slept less during the dark period. New microglia also had a different shape than microglia in control mice. We conclude that microglia are necessary to regulate sleep after an inflammatory challenge. ABSTRACT: Microglia play a critical role in the neuroimmune response, but little is known about the role of microglia in sleep following an inflammatory trigger. Nevertheless, decades of research have been predicated on the assumption that an inflammatory trigger increases sleep through microglial activation. We hypothesized that mice (n = 30) with depleted microglia using PLX5622 (PLX) would sleep less following the administration of lipopolysaccharide (LPS) to induce inflammation. Brains were collected and microglial morphology was assessed using quantitative skeletal analyses and physiological parameters were recorded using non-invasive piezoelectric cages. Mice fed PLX diet had a transient increase in sleep that dissipated by week 2. Subsequently, following a first LPS injection (0.4 mg/kg), mice with depleted microglia slept more than mice on the control diet. All mice were returned to normal rodent chow to repopulate microglia in the PLX group (10 days). Nominal differences in sleep existed during the microglia repopulation period. However, following a second LPS injection, mice with repopulated microglia slept similarly to control mice during the dark period but with longer bouts during the light period. Comparing sleep after the first LPS injection to sleep after the second LPS injection, controls exhibited temporal changes in sleep patterns but no change in cumulative minutes slept, whereas cumulative sleep in mice with repopulated microglia decreased during the dark period across all days. Repopulated microglia had a reactive morphology. We conclude that microglia are necessary to regulate sleep after an immune challenge.