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Vancomycin Pretreatment on MPTP-Induced Parkinson’s Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut

MPTP公司 药理学 黑质 神经炎症 神经保护 多巴胺 肠道菌群 阿克曼西亚 TLR4型 万古霉素 化学 炎症 医学 内分泌学 生物 内科学 生物化学 多巴胺能 乳酸菌 发酵 金黄色葡萄球菌 细菌 遗传学
作者
Chun Cui,Hui Hong,Yun Shi,Yu Zhou,Chen-Meng Qiao,Weijiang Zhao,Liping Zhao,Jian Wu,Wei Quan,Gu-Yu Niu,Yibo Wu,Chao-Sheng Li,Cheng Li,Yan Hong,Yan‐Qin Shen
出处
期刊:Journal of Neuroimmune Pharmacology [Springer Nature]
卷期号:18 (1-2): 72-89 被引量:26
标识
DOI:10.1007/s11481-021-10047-y
摘要

A growing body of evidence implies that gut microbiota was involved in pathogenesis of Parkinson's disease (PD), but the mechanism is still unclear. The aim of this study is to investigate the effects of antibiotics pretreatment on the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. In this study, vancomycin pretreatment was given by gavage once daily with either vancomycin or distilled water for 14 days to mice, then mice were administered with MPTP (20 mg/kg, i.p) for four times in one day to establish an acute PD model. Results show that vancomycin pretreatment significantly improved motor dysfunction of mice in pole and traction tests. Although vancomycin pretreatment had no effect on dopamine (DA) or the process of DA synthesis, it inhibited the metabolism of DA by suppressing the expression of striatal monoamine oxidase B (MAO-B). Furthermore, vancomycin pretreatment reduced the number of astrocytes and microglial cells in the substantia nigra pars compacta (SNpc) to alleviate neuroinflammation, decreased the expression of TLR4/MyD88/NF-κB/TNF-α signaling pathway in both brain and gut. Meanwhile, vancomycin pretreatment changed gut microbiome composition and the levels of fecal short chain fatty acids (SCFAs). The abundance of Akkermansia and Blautia increased significantly after vancomycin pretreatment, which might be related to inflammation and inhibition of TLR4 signaling pathway. In summary, these results demonstrate that the variation of gut microbiota and its metabolites induced by vancomycin pretreatment might decrease dopamine metabolic rate and relieve inflammation in both gut and brain via the microbiota-gut-brain axis in MPTP-induced PD mice. The neuroprotection of vancomycin pretreatment on MPTP-induced Parkinson's disease mice The alterations of gut microbiota and SCFAs induced by vancomycin pretreatment might not only improve motor dysfunction, but also decrease dopamine metabolism and relieve inflammation in both brain and gut via TLR4/MyD88/NF-κB/TNF-α pathway in MPTP-induced PD mice.
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