Swift Kevin M, Gary Nicholas C, Urbanczyk Phillip J
Medical Readiness Systems Biology Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
Front Neurosci. 2024 Aug 29;18:1426189. doi: 10.3389/fnins.2024.1426189. eCollection 2024.
The recurrent hormonal fluctuations within reproductive cycles impact sleep-wake behavior in women and in rats and mice used in preclinical models of sleep research. Strides have been made in sleep-related clinical trials to include equal numbers of women; however, the inclusion of female rodents in neuroscience and sleep research is lacking. Female animals are commonly omitted from studies over concerns of the effect of estrus cycle hormones on measured outcomes. This review highlights the estrous cycle's broad effects on sleep-wake behavior: from changes in sleep macroarchitecture to regionally specific alterations in neural oscillations. These changes are largely driven by cycle-dependent ovarian hormonal fluctuations occurring during proestrus and estrus that modulate neural circuits regulating sleep-wake behavior. Removal of estrous cycle influence by ovariectomy ablates characteristic sleep changes. Further, sex differences in sleep are present between gonadally intact females and males. Removal of reproductive hormones via gonadectomy in both sexes mitigates some, but not all sex differences. We examine the extent to which reproductive hormones and sex chromosomes contribute to sex differences in sleep-wake behavior. Finally, this review addresses the limitations in our understanding of the estrous cycle's impact on sleep-wake behavior, gaps in female sleep research that are well studied in males, and the implications that ignoring the estrous cycle has on studies of sleep-related processes.
生殖周期中反复出现的激素波动会影响女性以及用于睡眠研究临床前模型的大鼠和小鼠的睡眠-觉醒行为。在与睡眠相关的临床试验中已取得进展，纳入了数量相等的女性；然而，在神经科学和睡眠研究中缺少对雌性啮齿动物的纳入。出于对发情周期激素对测量结果影响的担忧，雌性动物通常被排除在研究之外。本综述强调了发情周期对睡眠-觉醒行为的广泛影响：从睡眠宏观结构的变化到神经振荡的区域特异性改变。这些变化很大程度上是由发情前期和发情期出现的依赖于周期的卵巢激素波动驱动的，这些波动调节着控制睡眠-觉醒行为的神经回路。通过卵巢切除术消除发情周期的影响可消除特征性的睡眠变化。此外，性腺完整的雌性和雄性之间存在睡眠方面的性别差异。两性通过性腺切除术去除生殖激素可减轻部分但并非全部性别差异。我们研究了生殖激素和性染色体在睡眠-觉醒行为性别差异中所起作用的程度。最后，本综述探讨了我们在理解发情周期对睡眠-觉醒行为影响方面的局限性、在雄性中已得到充分研究而在雌性睡眠研究中存在的差距，以及忽视发情周期对睡眠相关过程研究的影响。
