School of Life Sciences, South China Normal University, Guangzhou, 510631, PR China.
Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, PR China; South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research, Panyu Central Hospital, Guangzhou, 511400, PR China.
Brain Res Bull. 2021 Sep;174:41-52. doi: 10.1016/j.brainresbull.2021.05.028. Epub 2021 Jun 2.
Sleep deprivation (SD) is a hallmark of modern society and associated with many neuropsychiatric disorders, including depression and anxiety. However, the cellular and molecular mechanisms underlying SD-associated depression and anxiety remain elusive. Does the neuroinflammation play a role in mediating the effects of SD? In this study, we investigated SD-induced cellular and molecular alterations in the hippocampus and asked whether treatment with an anti-inflammatory drug, minocycline, could attenuate these alterations. We found that SD animals exhibit activated microglia and decreased levels of Keap1 and Nrf2 (antioxidant and anti-inflammatory factors) in the hippocampus. In vivo local field potential recordings show decreased theta and beta oscillations, but increased high gamma oscillations, as a result of SD. Behavioral analysis revealed increased immobility time in the forced swim and tail suspension tests, and decreased sucrose intake in SD mice, all indicative of depressive-like behavior. Moreover, open field test and elevated plus maze test results indicated that SD increases anxiety-like behavior. Interestingly, treatment with the microglial modulator minocycline prevented SD-induced microglial activation, restored Keap1 and Nrf2 levels, normalized neuronal oscillations, and alleviated depressive-like and anxiety-like behavior. The present study reveals that microglial activation and Keap1-Nrf2 signaling play a crucial role in SD-induced behavioral alteration, and that minocycline treatment has a protective effect on these alterations.
睡眠剥夺（SD）是现代社会的一个标志，与许多神经精神疾病有关，包括抑郁症和焦虑症。然而，SD 相关的抑郁症和焦虑症的细胞和分子机制仍不清楚。神经炎症是否在介导 SD 的影响中发挥作用？在这项研究中，我们研究了 SD 诱导的海马体中的细胞和分子变化，并询问了抗炎药物米诺环素的治疗是否可以减轻这些变化。我们发现，SD 动物的海马体中存在活化的小胶质细胞和 Keap1 和 Nrf2（抗氧化和抗炎因子）水平降低。体内局部场电位记录显示，由于 SD，θ和β振荡减少，而高γ振荡增加。行为分析显示强迫游泳和悬尾试验中的不动时间增加，SD 小鼠的蔗糖摄入量减少，所有这些都表明存在抑郁样行为。此外，旷场试验和高架十字迷宫试验结果表明，SD 增加焦虑样行为。有趣的是，小胶质细胞调节剂米诺环素的治疗可预防 SD 诱导的小胶质细胞活化，恢复 Keap1 和 Nrf2 水平，使神经元振荡正常化，并缓解抑郁样和焦虑样行为。本研究表明，小胶质细胞活化和 Keap1-Nrf2 信号转导在 SD 诱导的行为改变中起着至关重要的作用，米诺环素治疗对这些改变具有保护作用。
