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

描述（由申请人提供）：睡眠不足的女性比睡眠不足的男性有更高的心血管疾病，肥胖和代谢失调的发生率。性别对从睡眠不足中恢复的能力的影响可能是女性发病风险增加的基础。因此，确定导致从睡眠不足中恢复能力的性别差异的因素对于减少甚至消除这种差异至关重要。 睡眠健康的性别差异我们已经证明，小鼠每日睡眠量的性别差异取决于循环生殖激素，并且通过增加睡眠量和改变SWA从睡眠损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睡眠不足中恢复的能力。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）男性和女性长期慢性睡眠丧失的多导睡眠图睡眠反应。这些限制强调了需要有效的动物模型来确定性别特异性遗传和激素相互作用是否会影响慢性睡眠丧失期间和之后的睡眠机会。一个令人兴奋的遗传性别小鼠模型现在提供了一个机会，检查性染色体的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小鼠模型中，性染色体补体与性腺和表型性别相反。此外，改进的能力，以获得皮质内记录的慢波活动（SWA）在活跃的啮齿类动物现在提供了一个独特的机会，以确定性别的调节影响的稳态睡眠反应。通过采用更严格的电生理测量SWA，并通过检查性染色体补体是否对慢性睡眠丧失破坏睡眠调节机制的能力有影响，这些研究将确定慢性睡眠丧失引起的睡眠改变的性别差异的性质，并增加对这些差异的机制的理解。

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.