Cellular Mechanisms for the hormonal Modulation of Sleep

描述(申请人提供)：为了保持健康，高质量的睡眠是必不可少的。患有睡眠障碍的人不仅会感到疲惫，还会损害记忆和学习，增加压力和焦虑，并降低日常生活质量。睡眠障碍在女性中的普遍程度是男性的两倍。在雌激素水平显著下降的绝经期，女性抱怨失眠、睡眠障碍、难以入睡和疲惫的情况急剧增加。包括人类在内的许多不同物种的研究表明，性激素(雌激素、孕激素和雄激素)会影响睡眠的生理和病理。然而，荷尔蒙影响睡眠行为的分子和细胞机制尚不清楚。这项提议旨在研究荷尔蒙影响睡眠的潜在分子途径。在这方面，老鼠是一个有价值的模型，因为已经获得了关于一般睡眠模式的广泛知识。这项建议的目标是研究雌二醇在调节睡眠/觉醒行为的细胞和分子机制中的作用。我们假设性类固醇对睡眠模式的影响是由类固醇诱导的变化介导的-信号化合物，如前列腺素D2和伽马氨基丁酸(GABA)在参与睡眠和觉醒调节的关键脑核中的表达。 大量睡眠调查报告称，女性的睡眠问题比男性要多得多。然而，荷尔蒙对睡眠稳态的调节是一个严重缺乏代表性的研究领域。事实上，2003年修订的《国家睡眠障碍研究计划》指出，需要加强努力，以更好地了解睡眠的神经生理学和女性睡眠障碍的神经病理，还需要进行更多的基础科学研究，解决睡眠中性激素调节的机制。这项研究的潜在发现将促进我们对类固醇相关的睡眠控制以及激素功能变化如何导致睡眠病理的理解，这些疾病在女性中一直与情绪障碍有医学上的关联。

DESCRIPTION (provided by applicant): Quality sleep is imperative for the maintenance of good health. Persons suffering from sleep disturbances are not only fatigued but have impaired memory and learning, increased stress and anxiety and decreased quality of daily life. Sleep disturbances are twice as common among women compared to men. Complaints by women of insomnia, disturbed sleep, difficulty returning to sleep and fatigue rise sharply during their menopausal years when estrogen levels decrease markedly. Studies from a number of different species, including humans, suggest that sex hormones (estrogens, progestins and androgens) influence the physiology and pathology of sleep. However, the molecular and cellular mechanisms by which hormones act to influence sleep behavior are unknown. This proposal seeks to investigate potential molecular pathways through which hormones influence sleep. The rat serves as a valuable model in this regard because of the extensive knowledge on general sleep patterns already gained. The goal of this proposal seeks to investigate the role of estradiol in the modulation of the cellular and molecular mechanisms underlying sleep/wake behavior. We hypothesize that the effect of sex steroids on sleep patterns is mediated by steroid-induced changes - the expression of signaling compounds, such as prostaglandin D2 and gamma-amino butyric acid (GABA), in key brain nuclei that are involved in the regulation of sleep and wakefulness. Numerous sleep surveys report women experience considerably more sleep problems than men. However, hormonal modulation of sleep homeostasis is a severely unrepresented area of research. In fact, the 2003 revision of the National Sleep Disorders Research Plan indicated that "enhanced efforts are needed to better understand the neurophysiology of sleep and the neuropathology of sleep disorders in women" and that more basic science research addressing the mechanism of sex hormone modulation of sleep is needed. The potential findings of this research will advance our understanding of steroid associated control of sleep and how changes in hormonal function lead to sleep pathologies, which in women have been medically correlated with mood disorders.