Sleep loss leads to a spectrum of mood disorders such as anxiety disorders, bipolar disorder and depression in many individuals. However, the underlying mechanisms are largely unknown. In this study, sleep-disturbed animals were tested for anxiety and depressive behaviors. We then studied the effects of SD on hypothalamic-pituitary-adrenal (HPA) axis function by measuring serum and CSF levels of corticosterone (CORT), and at the end of the experiment, brains were collected to measure the circadian oscillations of clock genes expression in the hypothalamus, glial cell activation and inflammatory cytokine alterations. Our results indicated that SD for 3 days resulted in anxiety- and depressive-like behaviors. SD exaggerated cortisol response to HPA axis, significantly altered the circadian oscillations of clock genes, decreased the expression of tight junction protein ZO-1 and Claudin 5 and increased the number of GFAP-positive cells and Iba-1-positive cells and caused subsequent elevation of pro-inflammatory cytokines IL-6, IL-1β and TNFα. These findings demonstrated that SD for 3 days induced anxiety- and depression-like behaviors in rats in company with altering the circadian oscillations of clock genes and inducing neuroinflammation, indicating the underlying mechanism of sleep loss induced neuronal dysfunction.

许多人的睡眠不足会导致一系列情绪障碍，例如焦虑症、双相情感障碍和抑郁症。然而，潜在的机制在很大程度上是未知的。在这项研究中，对睡眠障碍动物的焦虑和抑郁行为进行了测试。然后我们通过测量血清和脑脊液皮质酮 (CORT) 水平研究 SD 对下丘脑-垂体-肾上腺 (HPA) 轴功能的影响，并在实验结束时收集大脑以测量时钟基因表达的昼夜节律振荡在下丘脑，胶质细胞活化和炎性细胞因子改变。我们的结果表明，连续 3 天的 SD 会导致类似焦虑和抑郁的行为。SD 夸大了皮质醇对 HPA 轴的反应，显着改变了时钟基因的昼夜节律振荡，降低紧密连接蛋白 ZO-1 和 Claudin 5 的表达，增加 GFAP 阳性细胞和 Iba-1 阳性细胞的数量，并导致随后的促炎细胞因子 IL-6、IL-1β 和 TNFα 升高。这些发现表明，持续 3 天的 SD 会在大鼠中诱导焦虑和抑郁样行为，同时改变时钟基因的昼夜节律振荡并诱导神经炎症，表明睡眠不足导致神经元功能障碍的潜在机制。