Cellular Mechanisms for the hormonal Modulation of Sleep

描述（由申请人提供）：高质量的睡眠对保持身体健康至关重要。患有睡眠障碍的人不仅疲劳，而且记忆力和学习能力受损，压力和焦虑增加，日常生活质量下降。女性睡眠障碍的发生率是男性的两倍。在雌激素水平明显下降的绝经期，女性对失眠、睡眠紊乱、难以入睡和疲劳的抱怨急剧增加。对包括人类在内的许多不同物种的研究表明，性激素（雌激素、黄体酮和雄激素）影响睡眠的生理和病理。然而，激素影响睡眠行为的分子和细胞机制尚不清楚。这项提议旨在研究激素影响睡眠的潜在分子途径。在这方面，老鼠作为一个有价值的模型，因为我们已经获得了关于一般睡眠模式的广泛知识。本研究旨在探讨雌二醇在调节睡眠/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——信号化合物的表达，如前列腺素D2和γ -氨基丁酸（GABA），在关键的脑核中参与调节睡眠和觉醒。

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.