Department of Integrative Physiology, University of Colorado - Boulder, 2860 Wilderness Place, Boulder, CO, 80301, USA.
Department of Psychology and Neuroscience, University of Colorado - Boulder, Boulder, CO, USA.
Sci Rep. 2024 Oct 15;14(1):23622. doi: 10.1038/s41598-024-70996-1.
A significant effort in biomedical sciences has been made to examine relationships between sex and the mechanisms underlying various disease states and behaviors, including sleep. Here, we investigated biological sex differences in sleep using male and female C57BL/6J mice (n = 267). Physiological parameters were recorded for 48-h using non-invasive piezoelectric cages to determine total sleep, non-rapid eye movement (NREM) sleep, rapid eye movement (REM)-like sleep, and wakefulness (WAKE). We fit hierarchical generalized linear mixed models with nonlinear time effects and found substantial sex differences in sleep. Female mice slept less overall, with less NREM sleep compared to males. Females also exhibited more REM-like sleep and WAKE and had shorter NREM sleep bout lengths. We also conducted a simulation exercise where we simulated a hypothetical treatment that altered the sleep of female mice, but not male mice. In models that included an appropriate sex by treatment interaction, a female-specific treatment response was accurately estimated when sample sizes were equal but was not detected when sample sizes were unequal, and females were underrepresented. Failure to include both sexes in experimental designs or appropriately account for sex during analysis could lead to inaccurate translational recommendations in pre-clinical sleep studies.
生物医学科学领域做出了巨大努力，以研究性别与各种疾病状态和行为（包括睡眠）背后的机制之间的关系。在这里，我们使用雄性和雌性 C57BL/6J 小鼠（n=267）研究了睡眠中的生物学性别差异。使用非侵入性压电笼记录了 48 小时的生理参数，以确定总睡眠时间、非快速眼动 (NREM) 睡眠时间、快速眼动 (REM) 样睡眠时间和觉醒 (WAKE)。我们拟合了具有非线性时间效应的分层广义线性混合模型，发现睡眠存在显著的性别差异。雌性小鼠的总睡眠时间较短，与雄性相比，NREM 睡眠时间较少。雌性还表现出更多的 REM 样睡眠和觉醒，并且 NREM 睡眠的持续时间更短。我们还进行了一项模拟练习，模拟了一种改变雌性小鼠睡眠但不改变雄性小鼠睡眠的假设性治疗。在包含适当的性别与治疗相互作用的模型中，当样本量相等时，可以准确估计女性特异性的治疗反应，但当样本量不相等且女性代表性不足时，就无法检测到该反应。在实验设计中不包括两性或在分析中不适当考虑性别，可能会导致临床前睡眠研究中的不准确转化建议。
