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

从睡眠不足中恢复的能力存在性别差异：发育和性染色体剂量的作用

• 批准号: 10406178
• 负责人: Ketema N Paul
• 金额: $ 39.3万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406178
• 关键词: Adolescent; Adult; Animals; Area; Biological Markers; Birth; Brain; Chromosomes; Chronic; Complement component C1; Data; Development; Electrodes; Exhibits; Female; Feminization; Four Core Genotypes; Genes; Genetic; Goals; Gonadal Hormones; Gonadal Steroid Hormones; Health; Homeostasis; Hour; Implant; Incidence; Injections; Libido; Life; Link; Masculine; Modernization; Morbidity - disease rate; Mus; Neonatal; Organizational Change; Pathology; Pattern; Phase; Phenotype; Phenotypic Sex; Play; Ploidies; Predisposing Factor; Property; Recovery; Role; Severities; Sex Chromosomes; Sex Differences; Sexual Development; Sleep; Sleep Deprivation; Sleep Disorders Therapy; Sleep Fragmentations; Sleep disturbances; Slow-Wave Sleep; Societies; Testing; Testosterone Propionate; Woman; Work; X Chromosome; Y Chromosome; biological sex; dosage; experimental study; gene complementation; improved; male; men; mouse model; neonatal mice; neonate; non rapid eye movement; postnatal; prepuberty; pressure; reproductive development; response; sex; sleep regulation; sry Genes; testis determining factor

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.

项目摘要/摘要 每日睡眠量，睡眠碎片和基础慢波活动（SWA）的性别差异在很大程度上是 受性腺激素驱动。但是，中期睡眠量的性别差异和能力 从睡眠损失中恢复在很大程度上对性腺激素不敏感，并且部分受性别调节 染色体。本应用程序中的初步数据表明，活动中性别差异的关键决定因素 相位睡眠量是Y染色体的SRY基因的存在或不存在，该基因编码 睾丸确定的因素。这项研究将使用两种具有改变性染色体改变的小鼠线来阐明 睡眠中的性别差异的起源，以确定SRY基因和染色体的各自作用 补充睡眠调节机制。第一个特定目的将检验基因的假设 通过观察睡眠效果模式在发育过程中建立性别稳态的性别差异 成年小鼠的新生儿，青春期小鼠和脑电图的EMG，性别染色体改变和 激素。第二个特定目的将检验X染色体剂量驱动性别差异的假设 能够从睡眠损失中恢复。在每项研究中，小鼠的活动相睡眠量将 用作睡眠稳态的生物标志物。这些实验很重要，需要了解 睡眠体内平衡在调节睡眠中的作用及其建立方式。他们是第一个综合 分析少年哺乳动物物种中的性别差异，以及第一个检查的特定作用 睡眠时X或Y染色体剂量。这些实验的总体目标是确定 性别染色体和性相关基因能够调节睡眠的特定机制。这些 研究将揭示性稳态能力中性别差异的起源，从睡眠损失中恢复。这些 调查结果可能会导致改善睡眠障碍的疗法，这些疗法在发病率和 严重程度，尤其是那些在女性中更普遍的人。