Cellular Mechanisms for the hormonal Modulation of Sleep

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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.