Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Neurosci Lett. 2023 Jan 1;792:136940. doi: 10.1016/j.neulet.2022.136940. Epub 2022 Nov 3.
Sleep disturbances are common among disorders associated with hypothalamic pituitary-adrenal (HPA) axis dysfunction, such as depression and anxiety. This comorbidity may partly be the result of the intersection between the role of the HPA axis in mediating the stress response and its involvement in sleep-wake cyclicity. Our previous work has shown that following 20 h of sleep restriction, mice show a blunting of the HPA axis in response to an acute stressor. Furthermore, these responses differ in a sex-dependent manner. This study sought to examine the effect of sleep restriction on corticotropin-releasing factor (CRF)-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Male and female Crf-IRES-Cre: Ai14 (Tdtomato) reporter mice were sleep restricted for 20 h daily for either a single or three consecutive days using the modified multiple platform method. These mice allowed the visualization of CRF+ neurons throughout the brain. Animals were subjected to acute restraint stress, and their brains were collected to assess PVN neuronal activation via c-Fos immunohistochemistry. Analyses of cell counts revealed an ablation of the restraint-induced increase in both CRF/c-Fos colocalization and overall c-Fos expression in female mice following both a single day and three days of sleep restriction. Males showed an overall decrease in restraint-induced c-Fos levels following a single day of sleep restriction. However, male mice examined after three days of sleep restriction showed a recovery in PVN-CRF and overall PVN neuronal activation. These data suggest the sex dependent dysregulation in CRF function following sleep restriction.
睡眠障碍在与下丘脑-垂体-肾上腺 (HPA) 轴功能障碍相关的疾病中很常见，如抑郁症和焦虑症。这种共病可能部分是 HPA 轴在介导应激反应及其在睡眠-觉醒周期性中的作用的交叉结果。我们之前的工作表明，在 20 小时的睡眠限制后，小鼠对急性应激源的 HPA 轴反应会减弱。此外，这些反应在性别上存在差异。本研究旨在研究睡眠限制对下丘脑室旁核 (PVN) 中促肾上腺皮质释放因子 (CRF) 神经元的影响。雄性和雌性 Crf-IRES-Cre:Ai14 (Tdtomato) 报告小鼠每天使用改良的多平台方法限制睡眠 20 小时，持续 1 天或连续 3 天。这些小鼠允许在整个大脑中可视化 CRF+神经元。对动物进行急性束缚应激，收集其大脑，通过 c-Fos 免疫组织化学评估 PVN 神经元激活。细胞计数分析显示，在睡眠限制 1 天和 3 天后，雌性小鼠的 CRF/c-Fos 共定位和整体 c-Fos 表达均消除了束缚诱导的增加。雄性小鼠在睡眠限制 1 天后，整体束缚诱导的 c-Fos 水平下降。然而，在睡眠限制 3 天后检查的雄性小鼠显示 PVN-CRF 和整体 PVN 神经元激活恢复。这些数据表明，睡眠限制后 CRF 功能存在性别依赖性失调。
