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

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Title: Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut–microbiota–brain axis.
Authors: Pu, Yaoyu, Wu, Qiuhong, Zhang, Qiuping, Huang, Tianwen, Wen, Ji, Wei, Long, Hashimoto, Kenji, Liu, Yi
Source: Psychopharmacology. May2023, Vol. 240 Issue 5, p1103-1118. 16p. 1 Black and White Photograph, 1 Diagram, 6 Graphs.
Subjects: Mesenchymal stem cells, Neurotoxicology, Vesicles (Cytology), Gut microbiota, Methylphenyltetrahydropyridine, Parkinson's disease
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut–microbiota–brain axis.
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  Data: <searchLink fieldCode="AR" term="%22Pu%2C+Yaoyu%22">Pu, Yaoyu</searchLink><br /><searchLink fieldCode="AR" term="%22Wu%2C+Qiuhong%22">Wu, Qiuhong</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Qiuping%22">Zhang, Qiuping</searchLink><br /><searchLink fieldCode="AR" term="%22Huang%2C+Tianwen%22">Huang, Tianwen</searchLink><br /><searchLink fieldCode="AR" term="%22Wen%2C+Ji%22">Wen, Ji</searchLink><br /><searchLink fieldCode="AR" term="%22Wei%2C+Long%22">Wei, Long</searchLink><br /><searchLink fieldCode="AR" term="%22Hashimoto%2C+Kenji%22">Hashimoto, Kenji</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Yi%22">Liu, Yi</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. May2023, Vol. 240 Issue 5, p1103-1118. 16p. 1 Black and White Photograph, 1 Diagram, 6 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Mesenchymal+stem+cells%22">Mesenchymal stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Neurotoxicology%22">Neurotoxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Vesicles+%28Cytology%29%22">Vesicles (Cytology)</searchLink><br /><searchLink fieldCode="DE" term="%22Gut+microbiota%22">Gut microbiota</searchLink><br /><searchLink fieldCode="DE" term="%22Methylphenyltetrahydropyridine%22">Methylphenyltetrahydropyridine</searchLink><br /><searchLink fieldCode="DE" term="%22Parkinson's+disease%22">Parkinson's disease</searchLink>
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: May2023
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