Abstract
There are various sex differences in sleep/wake behaviors in mice. However, it is unclear whether there are sex differences in sleep homeostasis and arousal responses and whether gonadal hormones are involved in these sex differences. Here, we examined sleep/wake behaviors under baseline condition, after sleep deprivation by gentle handling, and arousal responses to repeated cage changes in male and female C57BL/6 mice that are hormonally intact, gonadectomized, or gonadectomized with hormone supplementation. Compared to males, females had longer wake time, shorter non-rapid eye movement sleep (NREMS) time, and longer rapid eye movement sleep (REMS) episodes. After sleep deprivation, males showed an increase in NREMS delta power, NREMS time, and REMS time, but females showed a smaller increase. Females and males showed similar arousal responses. Gonadectomy had only a modest effect on homeostatic sleep regulation in males but enhanced it in females. Gonadectomy weakened arousal response in males and females. With hormone replacement, baseline sleep in gonadectomized females was similar to that of intact females, and baseline sleep in gonadectomized males was close to that of intact males. Gonadal hormone supplementation restored arousal response in males but not in females. These results indicate that male and female mice differ in their baseline sleep–wake behavior, homeostatic sleep regulation, and arousal responses to external stimuli, which are differentially affected by reproductive hormones.
Highlights
Sleep is regulated in a homeostatic manner so that the drive for sleep becomes stronger after sleep deprivation, resulting in compensatory increases in sleep intensity and sleep amount (Franken et al, 2001; Suzuki A. et al, 2013)
Most of the studies have been conducted using male C57BL/6 mice, not female mice, and this male-biased research results may hinder the characterization of sexually dimorphic effects (Cahill, 2006), which may lead to an underestimation of risks for women, such as adverse reaction to drugs (Clayton and Collins, 2014), and it remains unclear whether the findings are specific to males or valid for both sexes
The present study shows sex differences in baseline sleep, the homeostatic regulation of sleep, and arousal response to a novel cage in C57BL/6 mice
Summary
Sleep is regulated in a homeostatic manner so that the drive for sleep becomes stronger after sleep deprivation, resulting in compensatory increases in sleep intensity and sleep amount (Franken et al, 2001; Suzuki A. et al, 2013). Paul et al (2006) showed that gonadectomy of male and female mice reduced sex difference in sleep under baseline condition and after sleep deprivation, and Paul et al (2009a) showed the effects of testosterone or estradiol supplementation on baseline sleep and NREMS delta power after sleep deprivation. It remains largely unclear whether there are sex differences in the homeostatic regulation of sleep and the arousal response to external stimuli and whether testosterone or estradiol supplementation can fully restore sleep changes caused by gonadectomy. Estrogen is generally thought to enhance wakefulness in mice and rats (Paul et al, 2009a; Mong and Cusmano, 2016), whether gonadal hormones are involved in homeostatic sleep regulation and arousal remains largely unknown
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