Sex differences in the ability to recover from sleep loss: the roles of development and sex chromosome dosage

项目摘要/摘要 在日常睡眠时间、睡眠碎片和基础慢波活动(SWA)方面存在很大的性别差异 由性腺激素驱动。然而，在中期活动期的睡眠时间和睡眠能力的性别差异 从失眠中恢复在很大程度上对性腺激素不敏感，部分受性调节 染色体。这项应用的初步数据显示，性别差异的一个关键决定因素是活跃的 睡眠时相量是指Y染色体Sry基因的存在或不存在，该基因编码 睾丸--决定因素。这项研究将使用两个性染色体改变的小鼠品系来阐明 睡眠中性别差异的起源及Sry基因和染色体各自的作用 补充睡眠调节机制。第一个明确的目标将检验Sry基因 通过观察睡眠-觉醒模式在发育过程中建立睡眠稳态的性别差异 新生、青春期前小鼠的肌电，以及性染色体和性染色体改变的成年小鼠的脑电/肌电 荷尔蒙。第二个具体目标将检验X染色体剂量导致性别差异的假设 从失眠中恢复的能力。在每一项研究中，小鼠的活跃期睡眠时间将 可作为睡眠动态平衡的生物标志物。这些实验很重要，需要理解 睡眠稳态在调节睡眠中的作用以及它是如何建立的。它们是第一个全面的 分析一种幼年哺乳动物的性别差异，并首次考察其特殊效应 X或Y染色体剂量对睡眠的影响。这些实验的首要目标是确定 性染色体和性相关基因能够调节睡眠的特定机制。这些 研究将揭示从失眠中恢复的体内平衡能力的性别差异的根源。这些 这些发现可能会导致改善睡眠障碍的治疗方法，这些睡眠障碍的发病率和性别差异 严重，特别是在妇女中更普遍的那些。

Project Summary/Abstract Sex differences in daily sleep amount, sleep fragmentation, and basal slow wave activity (SWA) are largely driven by gonadal hormones. However, sex differences in the mid-active phase sleep amount and the ability to recover from sleep loss are largely insensitive to gonadal hormones, and are regulated in part by sex chromosomes. Preliminary data in this application show that a key determinant of sex differences in active phase sleep amount is the presence or absence of the Sry gene of the Y chromosome, which encodes the testis-determining factor. This study will use two mouse lines with altered sex chromosomes to elucidate the origin of sex differences in sleep and in order to determine the respective roles of Sry gene and chromosome complement on sleep regulatory mechanisms. The first specific aim will test the hypothesis that Sry gene establishes sex differences in sleep homeostasis during development by observing sleep-wake patterns in the EMG of neonatal, prepubertal mice, and EEG/EMG of adult mice with altered sex chromosomes and hormones. The second specific aim will test the hypothesis that X chromosome dosage drives sex differences in the ability to recover from sleep loss. During each of these studies, active-phase sleep amount in mice will be used as a biomarker for sleep homeostasis. These experiments are important and required to understand the role of the sleep homeostat in regulating sleep and how it is established. They are the first comprehensive analysis of sex differences in a juvenile mammalian species and the first to examine the specific effects of either X or Y chromosome dosage on sleep. The overarching goal of these experiments is to identify the specific mechanisms through which sex chromosomes and sex-linked genes are able to regulate sleep. These studies will uncover the origins of sex differences in the homeostatic ability to recover from sleep loss. These findings will likely lead to improved therapies for sleep disorders that exhibit sex differences in incidence and severity, particularly those more prevalent in women.