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Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model
Published on: January 7, 2019
Antibiotic-induced microbiome depletion protects against MPTP-induced dopaminergic neurotoxicity in the brain
Yaoyu Pu1, Lijia Chang1, Youge Qu1
1Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Abstract:
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.
Insights
Antibiotic treatment protected mice from Parkinson's-like brain damage by altering gut microbes. This suggests the brain-gut axis plays a key role in neuroprotection against dopaminergic neurotoxicity.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- The brain-gut axis is implicated in Parkinson's disease pathogenesis.
- The specific role of gut microbiota in Parkinson's disease remains unclear.
Purpose of the Study:
- To investigate if antibiotic-induced microbiome depletion impacts dopaminergic neurotoxicity in a mouse model of Parkinson's disease.
- To explore the influence of the gut microbiome on neuroprotection.
Main Methods:
- Mice were treated with an antibiotic cocktail or water, followed by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
- Dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunoreactivity were assessed in mouse brains.
- Gut microbiota composition and diversity were analyzed using 16S rRNA sequencing.
Main Results:
- MPTP significantly reduced DAT and TH immunoreactivity in water-treated mice, indicating dopaminergic neurotoxicity.
- Antibiotic treatment prevented MPTP-induced reductions in DAT and TH.
- Antibiotic treatment altered gut microbiota diversity and composition, and MPTP further modified the microbiome in antibiotic-treated mice.
Conclusions:
- Antibiotic-induced microbiome depletion may offer protection against MPTP-induced dopaminergic neurotoxicity.
- These findings highlight the potential role of the brain-gut axis in modulating neurodegenerative processes in Parkinson's disease.
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