Sex-specific differences in psychophysiological stress-induced circadian sleep disruption and its impact on glucose metabolism in mice.

AIMS: Sex differences in the prevalence of chronic sleep disorders (CSD), including insomnia, have been documented. Questionnaire-based surveys generally report a higher prevalence in women, whereas polysomnographic assessments often indicate a higher prevalence in men. To elucidate sex differences in sleep disturbances and associated impairments in glucose metabolism, we employed a mouse model of CSD induced by psychophysiological stress.

METHODS: We evaluated the effects of one week of CSD under normal chow on activity and sleep-wake rhythms and six weeks of CSD under a high-fat high-sucrose (HFHS) diet on glucose metabolism in male and female mice.

KEY FINDINGS: Under normal chow with one week of CSD, reduced wheel-running activity during the dark phase was more pronounced in males. Both sexes exhibited decreased wakefulness and increased non-rapid eye movement (NREM) sleep during the dark phase; however, increased wakefulness during the light phase was more evident in males. Under prolonged CSD with HFHS feeding, males displayed more reductions in dark-phase activity and wakefulness, as well as greater increases in REM and NREM sleep compared with females. Notably, only males exhibited a significant reduction in slow-wave sleep throughout the light phase. Oral glucose tolerance testing revealed CSD-induced glucose intolerance in both sexes, whereas intraperitoneal glucose intolerance, insulin resistance, and decreased insulin secretion occurred exclusively in males.

SIGNIFICANCE: These findings demonstrate sex differences in psychophysiological stress-induced disruption of activity and sleep rhythms. Moreover, our results suggest sex-dependent mechanisms underlying glucose dysregulation associated with sleep disturbances, warranting further investigation into the molecular pathways.