Abstract
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.
Graphical Abstract
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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This study was supported by National Natural Science Foundation of China (82171429, 81771384, 81801276), Wuxi Municipal Health Commission (1286010241190480), Youth Foundation of Basic Research Program of Jiangnan University (JUSRP121063).
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The experiment design: Chun Cui, Hui Hong, Yan-Qin Shen; Establishment of MPTP model: Hui Hong, Yun Shi; Immunofluorescence and image analysis: Hui Hong, Chun Cui, Wei-Jiang Zhao, Wei Quan, Gu-Yu Niu; Behavioral test and feces collection: Hui Hong, Yu Zhou, Yun Shi; Western blot analysis and Enzyme-linked immunosorbent assay: Hui Hong, Wei Quan, Gu-Yu Niu, Yi-Bo Wu; Measurement of neurotransmitters and their metabolites and Analysis of short chain fatty acids in feces: Hui Hong, Yun Shi, Li-Ping Zhao, Yu Zhou, Chao-Sheng Li, Li Cheng; Statistical analysis: Chun Cui, Hui Hong, Jian Wu, Yan Hong; Interpretation and editing of manuscript: Chun Cui, Hui Hong, Yan-Qin Shen.
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Cui, C., Hong, H., Shi, Y. et al. Vancomycin Pretreatment on MPTP-Induced Parkinson’s Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut. J Neuroimmune Pharmacol 18, 72–89 (2023). https://doi.org/10.1007/s11481-021-10047-y
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DOI: https://doi.org/10.1007/s11481-021-10047-y