Twice Subacute MPTP Administrations Induced Time-Dependent Dopaminergic Neurodegeneration and Inflammation in Midbrain and Ileum, as Well as Gut Microbiota Disorders in PD Mice
Abstract
Parkinson's disease (PD) is a common progressive neurodegenerative disease. PD produces a pathological state in the intestine and disordered gut microbiota (GM), which may be important for the pathogenesis and progression of PD, but it is not clear. To explore the conditions and characteristics of intestinal pathology and GM disorders when PD-related injuries occur, we used twice 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subacute administration with an interval of 3 weeks (each was an intraperitoneal injection of 25 mg/kg MPTP for 5 consecutive days). We observed the changes in intestinal and brain immune status, intestinal barrier function and GM in different injury states one day, one week, and three weeks after the first stimulus and one day and one week after the second stimulus. Our study found that two subacute administrations of MPTP induced dopaminergic (DAergic) neuron injury and inflammation in the midbrain and ileum, impaired intestinal barrier function and GM disorders closely related to administration. These changes recovered after the first administration, but after repeated administration, some indicators showed more dramatic changes than during the first administration. Our results suggest that the intestinal tract is sensitive to PD-related injury, and the GM is susceptible to disturbances caused by intestinal function, which may be concerned in local immune disorders of the intestine.
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MPTP intervention drastically changed the intestinal microbiota of PD mice, increasing Bacteroides, Escherichia-Shigella, and Dubosiella, and decreasing Akkermansia.
“According to our research, MPTP intervention drastically changed the intestinal microbiota of PD mice (Figure 5), increasing Bacteroides, Escherichia-Shigella, and Dubosiella, and decreasing Akkermansia (Figure 5), which is consistent with the findings of previous studies [47,66,67].”
From Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease (2022) · cites this paper as [66]
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- Authors
- Xie, W., Gao, J., Jiang, R., Liu, X., Lai, F., Tang, Y., Xiao, H., Jia, Y., & Bai, Q.
- Affiliations
- Chongqing Medical University (CN)
- Jiulongpo Center for Disease Control and Prevention (CN)
- Corresponding author
- Bai, Qunhua
- Venue
- NeuroToxicology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 76
- Pages
- 200-212
- ISSN
- 0161-813X (ISSN-L)
- OpenAlex
- W2991453980
- Cited by
- 40
- References
- 61
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 5 · 2020: 2
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroToxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, MPTP, dopaminergic neuron loss, midbrain, ileum, intestinal inflammation, gut microbiota, intestinal barrier function, gut-brain axis, mouse model
- MeSH terms
- Gastrointestinal Microbiome, Animals, Disease Models, Animal, Dopamine, Encephalitis, Ileum, Male, Mesencephalon, Mice, Inbred C57BL, Parkinson Disease, Tyrosine 3-Monooxygenase, MPTP Poisoning, Dopaminergic Neurons
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