Table_2_The Role of Reproductive Hormones in Sex Differences in Sleep Homeostasis and Arousal Response in Mice.XLSX

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.

在雄性小鼠中，睡眠/觉醒行为存在多种性别差异。然而，关于睡眠稳态及觉醒反应是否存在性别差异，以及性腺激素是否参与其中，尚无定论。本研究旨在探讨在基础状态下、经温和处理导致的睡眠剥夺以及重复笼内环境变化刺激下，雌性及雄性C57BL/6小鼠（包括激素完整、去势及去势后补充激素的动物）的睡眠/觉醒行为和觉醒反应。与雄性小鼠相比，雌性小鼠的觉醒时间更长，非快速眼动睡眠（NREMS）时间更短，而快速眼动睡眠（REMS）阶段更长。睡眠剥夺后，雄性小鼠的NREMS delta功率、NREMS时间和REMS时间均有所增加，但雌性小鼠的增加幅度较小。雌雄小鼠的觉醒反应相似。去势对雄性小鼠的稳态睡眠调节作用有限，而在雌性小鼠中则增强了这种作用。去势削弱了雌雄小鼠的觉醒反应。激素替代疗法使得去势雌性小鼠的基础睡眠与激素完整雌性小鼠相似，去势雄性小鼠的基础睡眠则接近激素完整雄性小鼠。性腺激素补充疗法恢复了雄性小鼠的觉醒反应，但对雌性小鼠则无此效果。这些结果揭示了雄性小鼠和雌性小鼠在基础睡眠-觉醒行为、稳态睡眠调节以及对外部刺激的觉醒反应方面存在差异，这些差异受到生殖激素的不同影响。