Antibiotic-Induced Microbiome Depletion Protects against MPTP-Induced Dopaminergic Neurotoxicity in the Brain
Open accessAbstract
Although the brain-gut axis appears to play a role in the pathogenesis of Parkinson's disease, the precise mechanisms underlying the actions of gut microbiota in this disease are unknown. This study was undertaken to investigate whether antibiotic-induced microbiome depletion affects dopaminergic neurotoxicity in the mouse brain after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP significantly decreased dopamine transporter (DAT) immunoreactivity in the striatum and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra of water-treated mice. However, MPTP did not decrease DAT or TH immunoreactivity in the brains of mice treated with an antibiotic cocktail. Furthermore, antibiotic treatment significantly decreased the diversity and altered the composition of the host gut microbiota at the genus and species levels. Interestingly, MPTP also altered microbiome composition in antibiotic-treated mice. These findings suggest that antibiotic-induced microbiome depletion might protect against MPTP-induced dopaminergic neurotoxicity in the brain via the brain-gut axis.
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Treating MPTP-induced Parkinson's disease mice with a cocktail of broad-spectrum antibiotics (ampicillin, metronidazole, and neomycin sulfate) preserved tyrosine hydroxylase and dopamine transporter immunoreactivities, which are generally lost upon MPTP administration.
“treating mice where PD has been induced by MPTP with a cocktail of broad-spectrum antibiotics (ampicillin, metronidazole, and neomycin sulfate) was found to preserve TH and dopamine transporter immunoreactivities, which are generally lost upon MPTP administration [216]”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [216]
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References 58 · Cited by 80
- Authors
- Pu, Y., Chang, L., Qu, Y., Wang, S., Zhang, K., & Hashimoto, K.
- Affiliations
- Chiba University (JP)
- Corresponding author
- Hashimoto, Kenji
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2019-09-03
- Volume
- 11
- Issue
- 17
- Pages
- 6915-6929
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC6756889
- OpenAlex
- W2972212019
- Cited by
- 80
- References
- 58
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 15 · 2023: 14 · 2022: 18 · 2021: 11 · 2020: 8 · 2019: 1 · 2018: 1
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development (JP19dm0107119)
- Takase Scholarship Foundation
- Smoking Research Foundation (JP19dm0107119)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Parkinson's disease, gut microbiota, antibiotics, MPTP, dopaminergic neurotoxicity, gut-brain axis, dopamine transporter, tyrosine hydroxylase, substantia nigra, striatum, neuroprotection
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Bacterial Agents, Male, Mice, Inbred C57BL, Parkinson Disease, MPTP Poisoning, Dopaminergic Neurons
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