Tauroursodeoxycholic Acid Ameliorates Lipopolysaccharide-Induced Depression Like Behavior in Mice via the Inhibition of Neuroinflammation and Oxido-Nitrosative Stress
Tauroursodeoxycholic Acid Ameliorates Lipopolysaccharide-Induced Depression Like Behavior in Mice via the Inhibition of Neuroinflammation and Oxido-Nitrosative Stress
复制标题
牛磺熊去氧胆酸通过抑制神经炎症和氧化亚硝化应激改善脂多糖诱导的抑郁样行为
DOI：
10.1159/000494139
复制
发表时间：
2019-01-01
期刊：
影响因子：
3.1
通讯作者：
Chen, Zhuo
中科院分区：
文献类型：
--
作者：
Cheng, Li;Huang, Chao;Chen, Zhuo
抑郁症是一种精神疾病，会造成严重的经济和社会负担。抑郁症的发病机制在很大程度上仍不清楚。最近，神经炎症和氧化应激在抑郁症中的作用越来越受到关注。牛磺熊去氧胆酸 (TUDCA) 是一种临床可用药物，用于治疗胆固醇胆结石和保护神经元免受神经变性，据报道可以预防神经炎症和氧化应激。在这项研究中，我们研究了 TUDCA 对脂多糖 (LPS) 诱导的小鼠抑郁样行为、神经炎症和氧化亚硝化应激的影响。结果显示，TUDCA 预处理（每天一次，连续 7 天），剂量为 200 和 400 mg/kg，但不是 100 mg/kg，显着减弱了 LPS（0.83 mg/kg）引起的悬尾试验、强迫游泳试验和蔗糖偏好试验中的行为异常。进一步分析表明，TUDCA预处理（200、400 mg/kg）不仅抑制LPS刺激诱导的促炎细胞因子（如白细胞介素6和肿瘤坏死因子-a）的产生，而且减弱LPS触发的海马和前额皮质氧化亚硝化应激。综上所述，我们的结果提供了证据表明 TUDCA 可能是一种潜在的抗抑郁药，其抗抑郁机制可能与抑制大脑中的神经炎症反应和氧化亚硝化应激有关。 (C) 2018 S. Karger AG，巴塞尔
Depression is a mental disease that causes severe economic and social burdens. The mechanism for the onset of depression remains largely unknown. Recently, more and more attention is being given to the role of neuroinflammation and oxidative stress in depression. Tauroursodeoxycholic acid (TUDCA), a clinically available agent used to treat cholesterol gallstone and protect neurons against neurodegeneration, has been reported to prevent neuroinflammation and oxidative stress. In this study, we investigated the effect of TUDCA on lipopolysaccharide (LPS)-induced depression-like behavior, neuroinflammation, and oxido-nitrosative stress in mice. Results showed that TUDCA pretreatment (once daily for 7 consecutive days) at the dosage of 200 and 400 mg/kg, but not 100 mg/kg, markedly attenuated LPS (0.83 mg/kg)-induced behavioral abnormalities in the tail suspension test, forced swim test, and sucrose preference test. Further analysis showed that the TUDCA pretreatment (200, 400 mg/kg) not only inhibited the production of proinflammatory cytokines induced by LPS stimulation, such as interleukin-6 and tumor necrosis factor-a, but attenuated LPS-triggered oxido-nitrosative stress in the hippocampus and prefrontal cortex. Taken together, our results provide evidence to show that the TUDCA could be a potential antidepressant, and its antidepressive mechanism may be associated with the inhibition of the neuroinflammatory response and oxido-nitrosative stress in the brain. (C) 2018 S. Karger AG, Basel