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Oral Administration of Rotenone using a Gavage and Image Analysis of Alpha-synuclein Inclusions in the Enteric Nervous System
Published on: October 26, 2010
Fucoidan ameliorates rotenone-induced Parkinsonism in mice by regulating the microbiota-gut-brain axis
Xiaojing Yang1, Xuan Zhang1, Yufang Ma1
1National-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China.
Abstract:
Microbiota-gut-brain axis, the bidirectional relationship between the gut microbiota and the brain, has been increasingly appreciated in the pathogenesis of Parkinson's disease (PD). Fucoidan, a sulphate-rich polysaccharide, has been shown to be neuroprotective by reducing oxidative stress in PD models. However, the role of microbiota-gut-brain axis in the neuroprotective activity of fucoidan has not been revealed. In this study, the therapeutic effects of fucoidan and involvement of microbiota-gut-brain axis in rotenone (ROT)-induced PD were investigated. The results showed that fucoidan gavage attenuated neuroinflammation, dopamine neuronal damage and motor dysfunction in ROT-induced PD mice. In addition, fucoidan treatment ameliorated gut dysfunction, intestinal inflammation and disruption of the intestinal barrier in PD mice. Fucoidan also affected the composition of gut microbiota in PD mice, indicated particularly by decreased abundance of Akkermansia muciniphila and Lactobacillus johnsonii and increased abundance of Lactobacillus murinus. Mechanistic studies showed that fecal microbiota transplantation (FMT) from the fucoidan-treated mice and probiotic Lactobacillus murinus supplement are as potent as fucoidan treatment in attenuating peripheral and central inflammation and ameliorating dopamine neuronal damage, which might be attributed to the downregulation of LPS/TLR4/NF-κB signaling pathway. Our study suggests that fucoidan might be potential candidates for the treatment of PD.
Insights
Fucoidan treatment alleviates Parkinson's disease symptoms by reducing inflammation and dopamine neuron damage. This neuroprotection is linked to the gut microbiota-brain axis, suggesting fucoidan as a potential therapeutic agent for Parkinson's disease.
Area of Science:
- Neuroscience
- Microbiology
- Pharmacology
Background:
- The microbiota-gut-brain axis plays a crucial role in Parkinson's disease (PD) pathogenesis.
- Fucoidan exhibits neuroprotective effects by mitigating oxidative stress in PD models.
- The specific involvement of the microbiota-gut-brain axis in fucoidan's neuroprotective activity remains unclear.
Purpose of the Study:
- To investigate the therapeutic effects of fucoidan on rotenone (ROT)-induced Parkinson's disease (PD) in mice.
- To elucidate the involvement of the microbiota-gut-brain axis in fucoidan's neuroprotective mechanisms.
Main Methods:
- Induction of PD in mice using rotenone (ROT).
- Administration of fucoidan via gavage.
- Assessment of neuroinflammation, dopamine neuronal damage, motor function, gut health, and intestinal barrier integrity.
- Analysis of gut microbiota composition.
- Fecal microbiota transplantation (FMT) and probiotic supplementation (Lactobacillus murinus).
- Investigation of the LPS/TLR4/NF-κB signaling pathway.
Main Results:
- Fucoidan treatment attenuated neuroinflammation, dopamine neuronal damage, and motor dysfunction in ROT-induced PD mice.
- Fucoidan ameliorated gut dysfunction, intestinal inflammation, and intestinal barrier disruption.
- Fucoidan altered gut microbiota composition, decreasing Akkermansia muciniphila and Lactobacillus johnsonii while increasing Lactobacillus murinus.
- FMT from fucoidan-treated mice and Lactobacillus murinus supplementation mimicked fucoidan's therapeutic effects.
- These effects were associated with the downregulation of the LPS/TLR4/NF-κB signaling pathway.
Conclusions:
- Fucoidan demonstrates therapeutic potential for Parkinson's disease by modulating the microbiota-gut-brain axis.
- Fucoidan's neuroprotective effects involve reducing inflammation and dopamine neuronal damage, potentially via gut microbiota modulation.
- Fucoidan may represent a promising candidate for future Parkinson's disease treatments.
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