The impact of sex chromosomes on the ability to recover from sleep loss

描述(申请人提供)：与睡眠不足的男性相比，睡眠不足的女性患心血管疾病、肥胖和代谢紊乱的几率更高。性别对从失眠中恢复的能力的影响可能是导致女性发病风险增加的原因。因此，找出导致睡眠丧失后恢复能力的性别差异的因素，对于减少甚至有朝一日消除这种差异至关重要。 睡眠健康方面的性别差异。我们已经证明，小鼠每日睡眠量的性别差异依赖于循环中的生殖激素，通过增加睡眠量和改变SWA来从睡眠缺失中恢复的能力对这些激素相对不敏感。这一发现使我们假设，性染色体直接影响从失眠中恢复的能力。人类研究在以下方面的能力有限：1)遗传和表型性别对睡眠特征性别差异的贡献；2)多导睡眠图对男性和女性长期慢性睡眠缺失的反应。这些局限性强调了有效的动物模型的必要性，以确定在慢性睡眠丧失期间和之后，特定性别的遗传和荷尔蒙交互作用是否影响睡眠机会。一种令人兴奋的遗传性交小鼠模型现在提供了一个机会来检验性染色体对睡眠调节机制的离散贡献。在这个遗传性别的四个核心基因型鼠模型中，性染色体互补是性腺和表型性别的对立面。此外，在获得活跃啮齿动物皮层内慢波活动(SWA)记录的能力方面的改进，现在为确定性别对稳态睡眠反应的调节影响提供了一个独特的机会。通过对SWA采用更严格的电生理测量，并通过检验性染色体补充是否影响慢性睡眠缺失扰乱睡眠调节机制的能力，这些研究将确定慢性睡眠缺失引起的睡眠改变中性别差异的性质，并增加对这些差异背后的机制的理解。

DESCRIPTION (provided by applicant): Sleep-deprived women have higher rates of cardiovascular disease, obesity, and metabolic dysregulation than do sleep-deprived men. The influences of sex on the ability to recover from sleep loss may underlie these increased risks for morbidity in women. Identification of the factors that are responsible for sex differences in the ability to recover from sleep loss is therefore critical to reducing, and someday eliminating, this gender disparity in sleep health. We have shown that sex differences in the daily sleep amount of mice are dependent on circulating reproductive hormones and that the ability to recover from sleep loss by increasing sleep amount and altering SWA is relatively insensitive to these hormones. This finding led us to hypothesize that sex chromosomes directly influence the ability to recover from sleep loss. Human studies are limited in their ability to examine: 1) the contributions of genetic and phenotypic sex to gender differences in sleep traits and 2) polysomnographic sleep responses to extended chronic sleep loss in men and women. These limitations underscore the need for effective animal models to determine whether sex-specific genetic and hormonal interactions influence sleep opportunities during and after chronic sleep loss. An exciting mouse model of genetic sex now provides an opportunity to examine the discrete contributions of sex chromosomes to sleep regulatory mechanisms. In this four core genotype mouse model of genetic sex, the sex chromosome complement is the opposite of gonadal and phenotypic sex. In addition, refinements in the ability to obtain intracortical recording of slow wave activity (SWA) in active rodents now provide a unique opportunity to determine the regulatory influences of sex on homeostatic sleep responses. By employing a more rigid electrophysiological measurement of SWA and by examining whether sex chromosome complement has influences on the ability of chronic sleep loss to disrupt sleep regulatory mechanisms, these studies will determine the nature of sex differences in sleep alterations caused by chronic sleep loss and increase understanding of the mechanisms underlying those differences.