Human Umbilical Cord Mesenchymal Stem Cells Improve Locomotor Function in Parkinson's Disease Mouse Model Through Regulating Intestinal Microorganisms
Copyright © 2022 Sun, Gu, Xu, Zhao, Zhou, Zhou, Zhang, Wang, Han, Chai and An..
Parkinson's disease (PD) is a progressive neurological disorder characterized by loss of neurons that synthesize dopamine, and subsequent impaired movement. Umbilical cord mesenchymal stem cells (UC-MSCs) exerted neuroprotection effects in a rodent model of PD. However, the mechanism underlying UC-MSC-generated neuroprotection was not fully elucidated. In the present study, we found that intranasal administration of UC-MSCs significantly alleviated locomotor deficits and rescued dopaminergic neurons by inhibiting neuroinflammation in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a toxic agent which selectively destroys nigrostriatal neurons but does not affect dopaminergic neurons elsewhere). Furthermore, UC-MSC treatment altered gut microbiota composition characterized by decreased phylum Proteobacteria, class Gammaproteobacteria, family Enterobacteriaceae, and genus Escherichia-Shigella. In addition, the neurotransmitter dopamine in the striatum and 5-hydroxytryptamine in the colon were also modulated by UC-MSCs. Meanwhile, UC-MSCs significantly maintained intestinal goblet cells, which secrete mucus as a mechanical barrier against pathogens. Furthermore, UC-MSCs alleviate the level of TNF-α and IL-6 as well as the conversion of NF-κB expression in the colon, indicating that inflammatory responses were blocked by UC-MSCs. PICRUSt showed that some pathways including bacterial invasion of epithelial cells, fluorobenzoate degradation, and pathogenic Escherichia coli infection were significantly reversed by UC-MSCs. These data suggest that the beneficial effects were detected following UC-MSC intranasal transplantation in MPTP-treated mice. There is a possible neuroprotective role of UC-MSCs in MPTP-induced PD mice by cross talk between the brain and gut.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Frontiers in cell and developmental biology - 9(2021) vom: 22., Seite 808905 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Zhengqin [VerfasserIn] |
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| Links: |
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| Themen: |
Goblet cells |
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| Anmerkungen: |
Date Revised 08.02.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fcell.2021.808905 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Parkinson's disease (PD) is a progressive neurological disorder characterized by loss of neurons that synthesize dopamine, and subsequent impaired movement. Umbilical cord mesenchymal stem cells (UC-MSCs) exerted neuroprotection effects in a rodent model of PD. However, the mechanism underlying UC-MSC-generated neuroprotection was not fully elucidated. In the present study, we found that intranasal administration of UC-MSCs significantly alleviated locomotor deficits and rescued dopaminergic neurons by inhibiting neuroinflammation in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a toxic agent which selectively destroys nigrostriatal neurons but does not affect dopaminergic neurons elsewhere). Furthermore, UC-MSC treatment altered gut microbiota composition characterized by decreased phylum Proteobacteria, class Gammaproteobacteria, family Enterobacteriaceae, and genus Escherichia-Shigella. In addition, the neurotransmitter dopamine in the striatum and 5-hydroxytryptamine in the colon were also modulated by UC-MSCs. Meanwhile, UC-MSCs significantly maintained intestinal goblet cells, which secrete mucus as a mechanical barrier against pathogens. Furthermore, UC-MSCs alleviate the level of TNF-α and IL-6 as well as the conversion of NF-κB expression in the colon, indicating that inflammatory responses were blocked by UC-MSCs. PICRUSt showed that some pathways including bacterial invasion of epithelial cells, fluorobenzoate degradation, and pathogenic Escherichia coli infection were significantly reversed by UC-MSCs. These data suggest that the beneficial effects were detected following UC-MSC intranasal transplantation in MPTP-treated mice. There is a possible neuroprotective role of UC-MSCs in MPTP-induced PD mice by cross talk between the brain and gut | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Parkinson’s disease (PD) | |
| 650 | 4 | |a goblet cells | |
| 650 | 4 | |a gut microbiota | |
| 650 | 4 | |a human umbilical cord mesenchymal stem cells | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a neurotransmitter | |
| 700 | 1 | |a Gu, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Hongjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yongjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Luyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhongxia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wenting |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Chai, Xiqing |e verfasserin |4 aut | |
| 700 | 1 | |a An, Shengjun |e verfasserin |4 aut | |
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