A night of broken sleep usually leaves people foggy and short-tempered, yet the body still holds its core temperature steady, keeps metabolism on schedule, and keeps the immune system ready. That quiet stability is not automatic. New research from the University of Colorado Boulder points to an unlikely crew doing much of the work: microglia, the brain’s resident immune cells. When they were removed in mice, body temperature drifted, sleep fell apart in sex-specific ways, and the damage only became fully visible once sleep itself was fragmented.
The brain’s resident immune cells
Microglia have long been cast as the brain’s cleanup crew. They prune synapses, clear dead cells, and respond to injury. But they also sit at a strategic intersection: between the immune system and the hypothalamus, the structure that runs both thermoregulation and the sleep-wake cycle. That position makes microglia a plausible bridge between two systems that are tightly coupled yet usually studied separately.
The study, published in Brain, Behavior, and Immunity, tested a specific hypothesis: microglia are required to keep both thermoregulation and sleep stable, both under ordinary conditions and when sleep is disrupted. The answer is that they are, and that they do the job differently in males and females.
What removing the custodians did
The team fed a CSF1R inhibitor called PLX5622 to 128 C57BL/6J mice, roughly half of each sex, clearing microglia from the brain. Implanted telemetry probes tracked core temperature continuously, first across a fortnight of depletion and then through a seven-day stretch of fragmented sleep. Multilevel statistical models then separated the contributions of the drug-laced diet, the animal’s sex, and the phase of the day.
The results diverged by sex from the start. In females, depletion raised body temperature during the first days of treatment, after which temperature normalized and later declined to pre-treatment baseline values. In males, PLX5622 barely moved the outcome metrics at all. The same manipulation, two very different physiological responses.
Fragmented sleep exposed the instability
The most striking finding emerged under stress. Across seven days of sleep fragmentation, mice without microglia ran cold, but at different times. Males showed hypothermia during the dark, active period, while females showed it during the light period. That time-of-day-specific hypothermia points to a larger idea: in an intact brain, microglia act as buffers that absorb the thermal disturbance created by broken sleep. Remove the buffers, and the latent instability that fragmentation causes becomes visible on the temperature trace.
That framing, microglia as homeostatic buffers under physiological stress, is one of the study’s central takeaways. It also recasts sleep fragmentation, often treated as a behavioral nuisance, as a physiological stressor that the brain’s immune cells actively defend against.
Sleep quantity is not sleep stability
The study also pulled apart two components of sleep usually discussed as one thing. In females, microglial depletion increased total sleep time. In males, it reduced the number of sleep-wake transitions, meaning sleep became more consolidated, with fewer interruptions. One sex slept more; the other slept more steadily.
The split suggests the amount of sleep and the steadiness of sleep are run by separate machinery, with microglia holding both levers and adjusting them differently by sex. It also echoes a broader theme in sleep research: measuring total sleep time alone can miss what is actually wrong with disrupted sleep.
The temperature-sleep link
Core temperature predicted sleep along a sharply curved relationship that held across every condition. Above roughly 35 degrees Celsius (95 degrees Fahrenheit), each additional degree was associated with 5 to 10 minutes less total sleep, an effect most pronounced during the dark, active period. The relationship held regardless of diet, which suggests temperature and sleep are mechanically coupled rather than merely correlated.
The finding gives the field a quantitative handle on a link sleep researchers have long suspected. It also suggests microglia modulate the temperature-dependent regulation of sleep itself, meaning the loss of microglia did not just disturb two systems in parallel, it disturbed the coupling between them.
Why it matters
Sleep fragmentation is routine in modern life: shift work, sleep apnea, newborn care, hospital wards, jet lag. If microglia help hold the line during broken sleep, then anything that compromises them, aging, chronic neuroinflammation, certain medications, may quietly raise vulnerability to thermal instability and sleep disruption at the same time.
The sex differences are just as important. Much preclinical sleep research has leaned on male animals, and this study shows the microglial contribution to sleep and temperature is fundamentally different in females. Sex is not a confound to control for; it is a variable that changes the answer.
The work also extends a long research tradition on immune-sleep interactions, a lineage that has shown for decades that immune signaling molecules can promote or suppress sleep. Microglia, it now appears, are a key node where that signaling meets everyday homeostasis. And it carries a practical warning: drugs that modulate or deplete microglia, including CSF1R inhibitors now used in some oncology trials, may have unappreciated effects on sleep and body temperature.
Limits
The study was done in an inbred mouse strain, and mice are not people. PLX5622 removes microglia wholesale rather than silencing specific functions, so the results show what happens without the cells, not exactly which microglial job matters most, and the drug can have effects beyond microglia. Sleep was inferred from telemetry-based behavioral measures rather than EEG-defined stages, which may miss finer architecture. The molecular pathway linking microglia to temperature, likely cytokine signaling through hypothalamic circuits, remains to be pinned down. Finally, the data are available on request rather than in a public repository.
Bottom line
Microglia are not just immune sentinels waiting for injury. They are everyday homeostatic regulators that help keep body temperature steady and sleep stable, and they perform that job differently in males and females. Sleep fragmentation unmasks their role. The takeaway reframes the sleeping brain as a neuroimmune organ, and suggests that broken sleep and thermal instability are two symptoms of the same underlying process.
Source
Steele N, Mannino GS, Green TRF, Beauregard LL, Szewczak M, Murphy SM, Opp MR, Rowe RK. Microglia regulate sleep and thermoregulatory stability. Brain Behav Immun. 2026 Jul 30:106937. doi:10.1016/j.bbi.2026.106937. PMID 42532441.