Table_1_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.

本研究旨在探讨小鼠在睡眠/觉醒行为方面的性别差异。尽管关于睡眠稳态与觉醒反应是否存在性别差异以及性腺激素是否参与这些性别差异尚无定论，本研究对未进行激素干预、阉割或阉割后补充激素的雄性及雌性C57BL/6小鼠在基础条件下、经轻柔处理导致的睡眠剥夺后，以及重复笼舍变动引起的觉醒反应进行了观察。相较于雄性小鼠，雌性小鼠的觉醒时间更长，非快速眼动睡眠（NREMS）时间更短，快速眼动睡眠（REMS）阶段更长。在睡眠剥夺后，雄性小鼠的NREMS delta功率、NREMS时间和REMS时间均有所增加，而雌性小鼠的增加幅度较小。雌雄小鼠在觉醒反应方面表现出相似性。阉割手术对雄性小鼠的睡眠稳态调节作用有限，但对雌性小鼠则有所增强。阉割手术减弱了雌雄小鼠的觉醒反应。激素替代治疗后，阉割雌性小鼠的基础睡眠模式与未阉割雌性小鼠相似，而阉割雄性小鼠的基础睡眠模式则接近于未阉割雄性小鼠。性腺激素补充疗法能够恢复雄性小鼠的觉醒反应，但对雌性小鼠则无此效果。这些研究结果揭示了雄性小鼠与雌性小鼠在基础睡眠-觉醒行为、睡眠稳态调节以及对外部刺激的觉醒反应方面存在差异，且这些差异受到生殖激素的调节作用。