Abstract

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.

Highlights

  • Parkinson’s disease (PD) is a common neurodegenerative disorder which occurs due to the loss of dopaminergic neurons

  • The growth curve indicated that the umbilical cord (UC)-Mesenchymal stem cells (MSCs) grew in an S-shaped curve (Figure 2C), and they continued to proliferate without being influenced by change medium, indicating that Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) had strong proliferation and self-renewal capabilities

  • This is the first study to determine the effect of UC-MSCs on microbial composition in MPTP-induced PD mouse model

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Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disorder which occurs due to the loss of dopaminergic neurons. The global prevalence of PD is predicted to be doubled by the year 2040 (Dorsey and Bloem, 2018), making it a faster growing neurodegenerative disorder than Alzheimer’s disease (Group, 2017). Microbiome normalization can improve impaired motor function in MPTP-induced PD mice (Zhou et al, 2019; Sun et al, 2021). These findings indicate that targeting the gut–brain axis is a promising strategy to treat PD

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