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Published on: September 22, 2023
Polymannuronic acid prevents dopaminergic neuronal loss via brain-gut-microbiota axis in Parkinson's disease model
Xiao-Li Dong1, Xiong Wang2, Fang Liu3
1Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Institute, Shenzhen, China; Food Safety and Technology Research Center, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong.
Abstract:
The study aims to investigate the potentially neuroprotective effects and underlying mechanisms for brown seaweed polysaccharide of polymannuronic acid (PM) against Parkinson's disease (PD) pathogenesis. PD model mice were pretreated with PM via oral gavage once per day for 4 weeks and the preventative effects of PM against neuronal loss together with its modulation on brain-gut-microbiota axis were systematically explored. The results showed PM administration improved motor functions by preventing dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) and enhanced contents of striatal homovanillic acid (HVA), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and γ-aminobutyric acid (GABA) in PD mice. PM significantly alleviated inflammation in gut, brain and systemic circulation as shown by reduced levels or expressions of pro-inflammatory cytokines concurrently and inhibited mitogen-activated protein kinases (MAPK) signaling pathway in mice colon. Meanwhile, PM greatly improved integrity of intestinal barrier and blood brain barrier (BBB) as indicated by increased expressions of tight junction associated proteins in both mice colon and SNpc. Further studies indicated PM treatment resulted in changes of gut microbial compositions, together with great alterations of digestion and metabolism of dietary proteins and fats, which led to surge increase of fecal short chain fatty acids (SCFAs) in the colon of PD mice. In conclusion, pre-administration of PM could provide neuroprotective effects against PD pathogenesis by suppressing inflammation in gut, brain and systemic circulation, and by improving integrity of intestinal barrier and BBB. PM might modulate brain-gut-microbiota axis, at least in part, via gut microbiota derived SCFAs as mediators.
Insights
Brown seaweed polysaccharide polymannuronic acid (PM) shows neuroprotective effects against Parkinson's disease (PD). PM improves motor function, reduces inflammation, and enhances gut barrier integrity, potentially via gut microbiota metabolites.
Area of Science:
- Neuroscience
- Pharmacology
- Microbiology
Background:
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss.
- The brain-gut-microbiota axis plays a crucial role in PD pathogenesis.
- Therapeutic strategies targeting inflammation and gut dysbiosis are of significant interest.
Purpose of the Study:
- To investigate the neuroprotective effects of polymannuronic acid (PM), a brown seaweed polysaccharide, against PD.
- To elucidate the underlying mechanisms of PM's action, focusing on the brain-gut-microbiota axis.
- To evaluate PM's impact on neuronal loss, inflammation, and gut barrier function in a PD mouse model.
Main Methods:
- PD model mice were orally administered PM for 4 weeks.
- Motor functions, dopaminergic neuronal survival, and neurotransmitter levels were assessed.
- Inflammation markers, gut and blood-brain barrier integrity, and gut microbial composition were analyzed.
- Mitogen-activated protein kinases (MAPK) signaling and short-chain fatty acids (SCFAs) were investigated.
Main Results:
- PM treatment improved motor functions and prevented dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc).
- PM administration enhanced levels of key neurotransmitters (HVA, 5-HT, 5-HIAA, GABA) in the striatum.
- PM significantly reduced inflammation in the gut, brain, and systemic circulation by inhibiting the MAPK pathway.
- PM improved intestinal and blood-brain barrier (BBB) integrity by upregulating tight junction proteins.
- PM altered gut microbial composition, increased fecal SCFAs, and modulated dietary protein/fat metabolism.
Conclusions:
- Polymannuronic acid (PM) exhibits significant neuroprotective effects against Parkinson's disease pathogenesis.
- PM alleviates neuroinflammation and improves gut and blood-brain barrier integrity.
- PM modulates the brain-gut-microbiota axis, potentially through gut microbiota-derived SCFAs, offering a promising therapeutic avenue for PD.
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