Neural mechanisms of gonadal steroid hormone effectsin circadian rhythmicity

女性患有一系列睡眠障碍，其中失眠和过度睡眠尤为常见。在许多情况下，这些睡眠障碍与内分泌变化密切相关，包括月经、怀孕和更年期。长期以来，人们一直推测，在这一时期发生的性激素水平的变化与这些睡眠-觉醒障碍密切相关。我们的目标是确定性腺类固醇背后的神经机制，特别是雌激素驱动的昼夜节律系统的变化。在本研究中，我们试图找出雌激素敏感振荡器(S)，它直接影响和导致雌性啮齿动物昼夜行为节律的改变。我们用免疫组织化学和发光记录方法检测了脑内几个靶区的时钟基因表达节律(PER2)，以测量体外循环PER2：：荧光素酶(PER2：：Luc)敲击小鼠组织外植体培养中PER2表达的昼夜节律。我们发现雌激素治疗直接影响下丘脑视前区的PER2：：LUC节律。最终，我们的发现将为女性睡眠障碍带来新的治疗方法，并改善女性整个生命周期的生活质量。

Women suffer from a range of sleep disorders with insomnia and hypersomnia being particularly common. In many cases, these sleep disorders are tightly associated with endocrine changes including menstruation, pregnancy, and menopause. It has been long speculated that variations of gonadalsteroid hormone levels that occur during this times are closely related to these sleep-wake disturbances. Our goalisto determine the neural mechanisms that underlie gonadal steroids, especially, estrogen driven changes in the circadian timing system. In this study, we tried to identify estrogen sensitive oscillator(s) which estrogen directly influences and lead to change circadian behavioral rhythm in female rodents. We examined rhythms of clock gene expression(PER2) in several target regions in the brainusing immunohistochemistry(in vivo) and luminescent recording methods to measure circadian rhythms of PER2 expression in tissue explant cultures from cycling PER2 :: LUCIFERASE(PER2 :: LUC) knockin mice(in vitro). We found that PER2 :: LUC rhythm in preoptic area(POA) of the hypothalamus was directly influenced by estrogen treatments. Ultimately, our findings will result in new therapeutic approaches for sleep disorders in women and improve the quality of life for women throughout their lifecycle.