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

性染色体对睡眠不足恢复能力的影响

• 批准号: 8640995
• 负责人: Ketema N Paul
• 金额: $ 30.38万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 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 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8640995
• 关键词: Accounting; Acute; Animal Model; Biological; Brain region; Cardiovascular Diseases; Chronic; Feeling; Female; Frequencies; Gender; Gene Expression; Genetic; Genetic Models; Genotype; Goals; Health; Hormonal; Hormones; Hour; Human; Immediate-Early Genes; Investigation; Lead; Measurement; Measures; Metabolic; Modeling; Morbidity - disease rate; Movement; Mus; Nature; Obesity; Phenotypic Sex; Placebos; Ploidies; Polysomnography; Predisposing Factor; Recovery; Reporting; Rest; Risk; Rodent; Safe Sex; Sex Characteristics; Sex Chromosomes; Sleep; Sleep Deprivation; Sleep disturbances; Societies; Technology; Testing; Wakefulness; Woman; X Chromosome; Y Chromosome; defined contribution; male; men; mortality; mouse model; mutant mouse model; pressure; prevent; relating to nervous system; reproductive hormone; research study; response; sex; therapeutic target; trait

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.

描述（由申请人提供）：与睡眠不足的男性相比，睡眠不足的女性患心血管疾病，肥胖和代谢失调的率更高。性别对从睡眠损失恢复能力的影响可能是女性发病风险增加的基础。因此，识别负责从睡眠损失恢复能力的性别差异的因素，对于减少和有一天消除，这是至关重要的 睡眠健康中的性别差异。我们已经表明，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从睡眠损失中恢复和改变SWA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损失中恢复的能力。人类研究的检查能力受到限制：1）遗传和表型性别对睡眠特征性别差异的贡献以及2）多个学术睡眠对男性和女性长期慢性睡眠损失的反应。这些局限性强调了有效的动物模型需要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。现在，令人兴奋的小鼠遗传性别模型为检查性染色体对睡眠调节机制的离散贡献提供了机会。在这四个核心基因型遗传性别模型中，性别染色体补体与性腺和表型性别相反。此外，在活性啮齿动物中获得慢波活动（SWA）的物质记录的能力的改进现在为确定性别对体内稳态睡眠反应的调节影响提供了独特的机会。通过对SWA进行更僵硬的电生理测量，并检查性染色体补体是否会影响慢性睡眠损失破坏睡眠调节机制的能力，这些研究将确定慢性睡眠丧失引起的性睡眠改变的性质，并增加对这些差异机制的理解。