Hydrogen sulfide antagonizes sleep deprivation-induced depression- and anxiety-like behaviors by inhibiting neuroinflammation in a hippocampal Sirt1-dependent manner
Hydrogen sulfide antagonizes sleep deprivation-induced depression- and anxiety-like behaviors by inhibiting neuroinflammation in a hippocampal Sirt1-dependent manner
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DOI：
10.1016/j.brainresbull.2021.10.002
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发表时间：
2021-10-16
影响因子：
3.8
通讯作者：
Tang, Xiao-Qing
中科院分区：
文献类型：
--
作者：
Kang, Xuan;Jiang, Li;Tang, Xiao-Qing
越来越多的证据证实，睡眠剥夺（SD），诱导海马神经炎症，是抑郁症的危险因素。硫化氢（H2S）是一种新型的神经调质，具有抗抑郁样作用。沉默交配型信息调节2同源物1（Sirt 1）是良好的特点，作为情绪障碍的调节器。此外，我们以前曾报道，硫化氢上调Sirt 1在SD暴露大鼠海马的表达。在这里，我们探讨了H2S是否改善抑郁和焦虑样行为以及海马神经炎症在SD暴露大鼠和Sirt 1是否介导H2S的这些保护作用。在目前的工作中，我们表明，NaHS（H2S供体）显著减轻SD暴露大鼠的抑郁和焦虑样行为，通过新颖性抑制喂养试验（NST）、强迫游泳试验（FST）、悬尾试验（TST）和高架十字迷宫试验（EPMT）测试，NaHS减轻SD暴露大鼠海马的神经炎症，如通过降低海马中促炎细胞因子（IL-1 β、IL-6和TNF-α）和趋化因子CCL 2的水平以及增加抗炎细胞因子（IL-4和IL-10）的水平所证明的。然而，Sirt 1抑制剂逆转了H2S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，H2S拮抗SD诱导的抑郁和焦虑样行为和神经炎症，这是海马Sirt 1所必需的。这些发现表明H2S是预防SD诱导的抑郁和焦虑的新方法。
Increasing evidence confirms that sleep deprivation (SD), which induces hippocampal neuroinflammation, is a risk factor for depression. Hydrogen sulfide (H2S) 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 H2S upregulates Sirt1 expression in the hippocampus of SD-exposed rats. Here, we explored whether H2S ameliorates depression-and anxiety-like behaviors as well as hippocampal neuroinflammatory in SD-exposed rats and whether Sirt1 mediates these protective roles of H2S. In the present work, we showed that NaHS (a donor of H2S) 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-1 beta, IL-6 and TNF-alpha) 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 H2S against SD-induced depression-and anxiety-like behaviors as well as hippocampal neuroinflammatory. In conclusion, H2S antagonizes SD-induced depression-and anxiety-like behaviors and neuroinflammation, which is required hippocampal Sirt1. These findings suggested that H2S is a novel approach to prevent SD-induced depression and anxiety.