The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China; Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China.
Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China; The Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China.
Brain Res Bull. 2021 Dec;177:194-202. doi: 10.1016/j.brainresbull.2021.10.002. Epub 2021 Oct 5.
Increasing evidence confirms that sleep deprivation (SD), which induces hippocampal neuroinflammation, is a risk factor for depression. Hydrogen sulfide (HS) is a novel neuromodulator that plays antidepressant-like role. Silent mating type information regulation 2 homolog 1 (Sirt1) is well-characterized as a regulator of mood disorder. Furthermore, we have previously reported that HS upregulates Sirt1 expression in the hippocampus of SD-exposed rats. Here, we explored whether HS ameliorates depression- and anxiety-like behaviors as well as hippocampal neuroinflammatory in SD-exposed rats and whether Sirt1 mediates these protective roles of HS. In the present work, we showed that NaHS (a donor of HS) significantly alleviated depression- and anxiety-like behaviors in the SD-exposed rats tested by novelty-suppressed feeding test (NST), forced swim test (FST), tail suspension test (TST), and elevated plus maze test (EPMT) and that NaHS attenuates neuroinflammatory in the hippocampus of SD-exposed rats, as evidenced by reducing the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and chemokine CCL2, as well as increasing the levels of anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. However, Sirt1 inhibitor reversed the protective effects of HS against SD-induced depression- and anxiety-like behaviors as well as hippocampal neuroinflammatory. In conclusion, HS antagonizes SD-induced depression- and anxiety-like behaviors and neuroinflammation, which is required hippocampal Sirt1. These findings suggested that HS is a novel approach to prevent SD-induced depression and anxiety.
越来越多的证据证实，睡眠剥夺（SD）会导致海马神经炎症，是抑郁的一个风险因素。硫化氢（HS）是一种新型的神经调质，具有抗抑郁作用。沉默交配型信息调节 2 同源物 1（Sirt1）是一种调节情绪障碍的物质。此外，我们之前曾报道过 HS 可上调 SD 暴露大鼠海马中的 Sirt1 表达。在这里，我们探讨了 HS 是否可以改善 SD 暴露大鼠的抑郁和焦虑样行为以及海马神经炎症，以及 Sirt1 是否介导了 HS 的这些保护作用。在本研究中，我们发现 NaHS（HS 的供体）可显著缓解 SD 暴露大鼠的抑郁和焦虑样行为，通过新奇抑制摄食试验（NST）、强迫游泳试验（FST）、悬尾试验（TST）和高架十字迷宫试验（EPMT）进行测试，并且 NaHS 可减轻 SD 暴露大鼠海马中的神经炎症，表现为降低促炎细胞因子（IL-1β、IL-6 和 TNF-α）和趋化因子 CCL2 的水平，以及增加海马中抗炎细胞因子（IL-4 和 IL-10）的水平。然而，Sirt1 抑制剂逆转了 HS 对 SD 诱导的抑郁和焦虑样行为以及海马神经炎症的保护作用。总之，HS 拮抗 SD 诱导的抑郁和焦虑样行为以及神经炎症，这需要海马 Sirt1。这些发现表明 HS 是预防 SD 诱导的抑郁和焦虑的一种新方法。
