Oxidative stress with mitochondrial defects has a central role in the development and deterioration of Multiple sclerosis (MS). According to new findings of the effects of metformin on mitochondrial function, has attracted a lot of attention. Furthermore, it is suggested that metformin exerts its beneficial influence through AMP-activated protein kinase (AMPK) pathway. In the current study, we investigated the possible protective effects of metformin on oxidative stress and mitochondrial function by activating the AMPK pathway in the cuprizone-induced demyelination. Mice were fed with cuprizone for 6 weeks. Animals simultaneously received metformin. After sacrificing animals, myelinations, and gliosis, changes in transcription factor and biochemical analysis were assessed. Transmission electron microscopy and luxol fast blue staining revealed that the myelinated axons within corpus callosum of cuprizone-induced demyelination animals increased after administration of metformin. Metformin also upregulated the expression of mitochondrial biogenesis genes. Furthermore, the biochemical analysis demonstrated that metformin ameliorated the oxidative stress induced by cuprizone. Immunohistochemistry analysis showed that astrogliosis and microgliosis were decreased after metformin administration while it enhanced the number of oligodendrocytes. Our data implicated that metformin exerts its therapeutic effects on MS by AMPK signaling improved mitochondrial homeostasis and protected oligodendrocytes.

中文翻译：

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二甲双胍通过AMPK的寡聚保护作用依赖于铜酮诱导的多发性硬化模型中线粒体止血的恢复。

具有线粒体缺陷的氧化应激在多发性硬化症（MS）的发展和恶化中起着核心作用。根据新发现的二甲双胍对线粒体功能的影响，引起了很多关注。此外，建议二甲双胍通过AMP激活的蛋白激酶（AMPK）途径发挥其有益作用。在当前的研究中，我们研究了二甲双胍可能通过激活铜酮诱导的脱髓鞘过程中的AMPK途径对氧化应激和线粒体功能的保护作用。给小鼠喂食铜酮6周。动物同时接受二甲双胍。处死动物，髓鞘形成和神经胶质变性后，评估转录因子的变化和生化分析。透射电镜和luxol固蓝染色显示，二甲双胍给药后，铜酮诱导的脱髓鞘动物的call体中的髓鞘轴突增加。二甲双胍还上调线粒体生物发生基因的表达。此外，生化分析表明二甲双胍改善了铜酮引起的氧化应激。免疫组织化学分析显示，二甲双胍给药后星形胶质细胞减少和小胶质细胞减少，而少突胶质细胞的数量增加。我们的数据暗示二甲双胍通过AMPK信号传导改善线粒体体内稳态和保护少突胶质细胞而对MS发挥治疗作用。