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Effect of CSF1R inhibitor on glial cells population and remyelination in the cuprizone model
Neuropeptides ( IF 2.9 ) Pub Date : 2021-07-13 , DOI: 10.1016/j.npep.2021.102179
Fatemeh Tahmasebi 1 , Shirin Barati 2 , Iraj Ragerdi Kashani 3
Affiliation  

Multiple sclerosis is a kind of autoimmune and demyelinating disease with pathological symptoms such as inflammation, myelin loss, astrocytosis, and microgliosis. The colony stimulating factor 1 receptor (CSF1R) is an essential factor for the microglial function, and PLX3397 (PLX) is its specific inhibitor. In this wstudy, we assessed the effect of different doses of PLX for microglial ablation on glial cell population and remyelination process. Sixty male C57BL/6 mice (8 weeks old) were divided into 6 groups. The animals were fed with 0.2% cuprizone diet for 12 weeks. For microglial ablation, PLX (290 mg/kg) was added to the animal food for 3, 7, 14 and 21 days. Glial cell population was measured using immunohistochemistry. The rate of remyelination was evaluated using electron microscopy and Luxol Fast Blue staining. The expression levels of all genes were assessed by qRT-PCR method. Data were analysed using GraphPad Prism and SPSS software. The results showed that the administration of different doses of PLX significantly reduced microglial cells (p ≤ .001). PLX administration also significantly increased oligodendrocytes population (p ≤ .001) and remyelination compared to the cuprizone mice, which was aligned with the results of LFB and TEM. Gene results showed that PLX treatment reduced CSF1R expression. According to the results, the administration of PLX for 21 days enhanced remyelination by increasing oligodendrocytes in the chronic demyelination model. These positive effects could be related to the reduction of microglia.



中文翻译:

CSF1R抑制剂对cuprizone模型中胶质细胞群和髓鞘再生的影响

多发性硬化是一种自身免疫性脱髓鞘疾病,具有炎症、髓鞘丢失、星形细胞增多、小胶质细胞增生等病理症状。集落刺激因子 1 受体 (CSF1R) 是小胶质细胞功能的重要因子,PLX3397 (PLX) 是其特异性抑制剂。在这项研究中,我们评估了不同剂量的 PLX 用于小胶质细胞消融对胶质细胞群和髓鞘再生过程的影响。将60只雄性C57BL/6小鼠(8周龄)分成6组。给动物喂食 0.2% 铜酮饲料 12 周。对于小胶质细胞消融,PLX (290 mg/kg) 添加到动物食品中 3、7、14 和 21 天。使用免疫组织化学测量胶质细胞群。使用电子显微镜和 Luxol Fast Blue 染色评估髓鞘再生率。通过qRT-PCR方法评估所有基因的表达水平。使用 GraphPad Prism 和 SPSS 软件分析数据。结果表明,给予不同剂量的PLX显着减少了小胶质细胞(p  ≤ .001)。与铜宗小鼠相比,PLX 给药还显着增加了少突胶质细胞数量 (p ≤ .001) 和髓鞘再生,这与 LFB 和 TEM 的结果一致。基因结果显示PLX处理降低了CSF1R的表达。根据结果​​,PLX 给药 21 天通过增加慢性脱髓鞘模型中的少突胶质细胞来增强髓鞘再生。这些积极作用可能与小胶质细胞的减少有关。

更新日期:2021-07-15
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