Journal Article

Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut–microbiota–brain axis

Wu, Qiuhong, Huang, Tianwen, Pu, Yaoyu, Zhang, Qiuping, Liu, Yi, Wei, Long, Wen, Ji, Hashimoto, Kenji

2023

Overview

Rationale Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder. Increasing evidence suggests the role of the gut–microbiota–brain axis in the pathogenesis of PD. Mesenchymal stem-cell-derived microvesicles (MSC-MVs) have emerged as a therapeutic potential for neurological disorders over the last years. Objective The objective of this study was to investigate whether MSC-MVs could improve PD-like neurotoxicity in mice after administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Results MPTP-induced reductions in the dopamine transporter and tyrosine hydroxylase expressions in the striatum and substantia nigra (SNr) were attenuated after a subsequent single administration of MSC-MVs. Increases in the phosphorylated α-synuclein (p-α-Syn)/α-Syn ratio in the striatum, SNr, and colon after MPTP injection were also attenuated after MSC-MVs injection. Furthermore, MSC-MVs restored MPTP-induced abnormalities of the gut microbiota composition. Interestingly, positive correlations between the genus Dubosiella and the p-α-Syn/α-Syn ratio were observed in the brain and colon, suggesting their roles in the gut–microbiota–brain communication. Moreover, MSC-MVs attenuated MPTP-induced reduction of the metabolite, 3,6-dihydroxy-2-[3-methoxy-4-(sulfooxy)phenyl]-7-(sulfinooxy)-3,4-dihydro-2H-1-benzopyran-5-olate, in the blood. Interestingly, a negative correlation between this compound and the p-α-Syn/α-Syn ratio was observed in the brain and colon. Conclusions These data suggest that MSC-MVs could ameliorate MPTP-induced neurotoxicity in the brain and colon via the gut–microbiota–brain axis. Therefore, MSC-MVs would have a new therapeutic potential for neurological disorders such as PD.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: alpha-Synuclein - metabolism / alpha-Synuclein - therapeutic use / Analysis / Animals / Biomedical and Life Sciences / Biomedicine / Brain - metabolism / Care and treatment / Colon / Composition / Diagnosis / Disease Models, Animal / Dopamine transporter / Gastrointestinal Microbiome / Genetic aspects / Gut microbiota / Intestinal microflora / Mice / Mice, Inbred C57BL / Microbiota / Microbiota (Symbiotic organisms) / Movement disorders / MPTP / MPTP Poisoning - metabolism / MPTP Poisoning - pathology / MPTP Poisoning - therapy / Neostriatum / Neurodegenerative diseases / Neurological diseases / Neurological disorders / Neurosciences / Neurotoxicity / Neurotoxicity syndromes / Original Investigation / Parkinson Disease - drug therapy / Parkinson's disease / Pharmacology/Toxicology / Psychiatry / Stem cells / Substantia nigra / Substantia Nigra - metabolism / Synuclein / Tyrosine 3-monooxygenase