Microglia regulate sleep and thermoregulatory stability

Area of Science:

• Neuroscience
• Immunology
• Sleep Science

Background:

• Sleep fragmentation disrupts physiological homeostasis, including thermoregulation and immune signaling.
• The cellular mechanisms stabilizing core body temperature and sleep architecture during disrupted sleep are poorly understood.
• Microglia, central nervous system immune cells, integrate neuroimmune signals with hypothalamic regulation of thermoregulation and sleep-wake control.

Purpose of the Study:

• To test the hypothesis that microglia are required to maintain thermoregulatory and sleep stability during physiological sleep and sleep fragmentation.
• To investigate the sex-dependent effects of microglial depletion on thermoregulation and sleep-wake behavior.

Main Methods:

• Pharmacological depletion of microglia using PLX5622 (PLX) in male and female C57BL/6J mice.
• Continuous core body temperature monitoring via telemetry devices.
• Assessment of sleep-wake behavior during a two-week depletion period and a subsequent 7-day sleep fragmentation paradigm.

Main Results:

• Microglial depletion induced sex- and diet-dependent alterations in thermoregulation and sleep.
• Sleep fragmentation with microglial depletion caused time-of-day-specific hypothermia.
• Microglial depletion dissociated sleep components sex-dependently: increased total sleep in females, but enhanced sleep consolidation in males.
• Core body temperature significantly predicted total sleep time, with higher temperatures reducing sleep, especially during the active period.

Conclusions:

• Microglia contribute to thermoregulatory processes and sleep stability in a sex-dependent manner.
• These findings support a neuroimmune framework where microglia coordinate thermoregulation and sleep.
• Microglial depletion is associated with dysregulation of both thermoregulation and sleep, underscoring their role in physiological homeostasis.