Effects of metformin on lipopolysaccharide-induced depressive-like behavior in mice and its mechanisms
Effects of metformin on lipopolysaccharide-induced depressive-like behavior in mice and its mechanisms
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二甲双胍对脂多糖诱导的小鼠抑郁样行为的影响及其机制
DOI：
10.1097/wnr.0000000000001401
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发表时间：
2020-01
期刊：
影响因子：
1.7
通讯作者：
Meng Xianfang
中科院分区：
文献类型：
--
作者：
Yang Sheng;Chen Xiaohe;Xu Yuanyuan;Hao Yan;Meng Xianfang
补充数字内容可在正文中找到。二甲双胍是一种AMPK激动剂，是治疗2型糖尿病的常用药物，被认为具有抗炎作用。已有研究表明，炎症在抑郁症的发病机制中起着重要作用。根据最近的研究，脂多糖(LPS)经常被用来诱导小鼠的抑郁样行为。然而，二甲双胍是否能缓解抑郁样行为的症状及其机制尚不清楚。本研究旨在观察二甲双胍是否能减轻脂多糖诱导的小鼠抑郁样行为，并探讨其机制。先给成年小鼠注射脂多糖(0.83 mg/kg，腹腔注射)，建立抑郁行为模型，连续24 ，分别给予或不给予二甲双胍。通过悬尾实验和强迫游泳实验检测二甲双胍对小鼠抑郁行为的影响。定量RT-PCR法检测Lcn-2及与炎症和Lcn-2相关的炎症分子IL-1β、IL-6和von Willebrand因子(VWF)的表达水平。结果表明，二甲双胍可逆转内毒素诱导的小鼠在悬尾实验和强迫游泳实验中的不动时间延长所致的类抑郁行为。研究还表明，内毒素可上调杏仁核组织中LcN-2mRNA和IL-1β等炎症相关分子的表达水平，二甲双胍可减轻这种作用。综上所述，二甲双胍通过调节LCN-2和炎症相关分子，包括IL-1β、IL-6和vWF的表达水平，减轻内毒素诱导的小鼠抑郁样行为。视频摘要：http://links.lww.com/WNR/A568
Supplemental Digital Content is available in the text. Metformin, an AMPK activator, is a widely used medicine for type II diabetes, which has been considered to exert the anti-inflammatory effects. It has been reported that inflammation plays an important role in the pathogenesis of depression. Lipopolysaccharide (LPS) is often utilized to induce depressive-like behavior in mice with respect to recent studies. However, whether metformin alleviates the symptoms of depressive-like behaviors and its mechanisms remain unexplored. The present study investigates whether metformin alleviates LPS-induced depressive-like behavior in mice and aims to explore the mechanisms. We first treated adult mice with LPS (0.83 mg/kg, intraperitoneal) to induce depressive-like behavior model for 24 hours after treatment with or without metformin. Then, the effects of metformin on depressive-like behaviors were detected by tail suspension test and forced swim test. Moreover, quantitative RT-PCR was used to determine the mRNA expression levels of lipocalin 2 (Lcn-2) and inflammatory molecules including IL-1β, IL-6 and von Willebrand factor (vWF), which are concerned with inflammation and Lcn-2. It was shown that LPS-induced mouse depressive-like behaviors, as indicated by the increased time of immobility in tail suspension test and forced swim test, were reversed by metformin. It was also shown that LPS increased the mRNA expression levels of Lcn-2 and inflammation-related molecules such as IL-1β in the amygdala tissue, which could be alleviated by metformin. Taken together, metformin mitigates LPS-induced depressive-like behavior in mice by regulating the expression level of Lcn-2 and inflammation-related molecules, including IL-1β, IL-6 and vWF. Video abstract: http://links.lww.com/WNR/A568
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DOI：
10.1016/j.bbr.2017.05.064
发表时间：
2017-05
期刊：
Behav Brain Res
影响因子：
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作者：
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