ArticleInternational journal of molecular sciences2022
Dual-Hit Model of Parkinson's Disease: Impact of Dysbiosis on 6-Hydroxydopamine-Insulted Mice-Neuroprotective and Anti-Inflammatory Effects of Butyrate.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- Implications of Butyrate Signaling Pathways on the Motor Symptomatology of Parkinson's Disease and Neuroprotective Effects-Therapeutic Approaches: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications.CNS & neurological disorders drug targets · 2024Pooled it
- Molecular Mechanisms of Obesity-Associated Oxidative Stress and Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Gut-Brain Signaling in Parkinson's Disease: A Narrative Review.International journal of molecular sciences · 2026Review
- The "Double-Hit" Model in Experimental Parkinsonism: Effects of Combined Exposure to Lactacystin and LPS.Bulletin of experimental biology and medicine · 2026Article
- Gut bacteria composition in animal models of Parkinson's disease: a systematic review and meta-analysis.NPJ Parkinson's disease · 2026Article
- Nervonic Acid fromBiomaterials research · 2026Article
- Examination of shared gut microbiome signatures in aging and Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Artificial intelligence empowers gut microbiota research in neurodegenerative diseases molecular mechanisms and precision therapy.iScience · 2025Review
- Butyrate-Mediated Upregulation of Insulin Pathway Gene Expression Suggests Potential Antidiabetic Effects.Drug development research · 2025Article
- Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach.International journal of molecular sciences · 2025Article
- From Obesity to Mitochondrial Dysfunction in Peripheral Tissues and in the Central Nervous System.Biomolecules · 2025Review
- Microbiota-Gut-Brain Axis in Age-Related Neurodegenerative Diseases.Current neuropharmacology · 2025Review
- Antibiotics-induced dysbiosis impacts dendritic morphology of adult mouse cortical interneurons.Frontiers in neuroanatomy · 2025Article
- Convergence of Neuroinflammation, Microbiota, and Parkinson's Disease: Therapeutic Insights and Prospects.International journal of molecular sciences · 2024Review
- The Gut Microbiome as a Catalyst and Emerging Therapeutic Target for Parkinson's Disease: A Comprehensive Update.Biomedicines · 2024Review
- Emerging Parameters Justifying a Revised Quality Concept for Cow Milk.Foods (Basel, Switzerland) · 2024Review
- Relationship Between Short-chain Fatty Acids and Parkinson's Disease: A Review from Pathology to Clinic.Neuroscience bulletin · 2024Review
- The aryl hydrocarbon receptor pathway: a linking bridge between the gut microbiome and neurodegenerative diseases.Frontiers in cellular neuroscience · 2024Review
- Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy.Epigenomics · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidence highlights Parkinson's disease (PD) initiation in the gut as the prodromal phase of neurodegeneration. Gut impairment due to microbial dysbiosis could affect PD pathogenesis and progression. Here, we propose a two-hit model of PD through ceftriaxone (CFX)-induced dysbiosis and gut inflammation before the 6-hydroxydopamine (6-OHDA) intrastriatal injection to mimic dysfunctional gut-associated mechanisms preceding PD onset. Therefore, we showed that dysbiosis and gut damage amplified PD progression, worsening motor deficits induced by 6-OHDA up to 14 days post intrastriatal injection. This effect was accompanied by a significant increase in neuronal dopaminergic loss (reduced tyrosine hydroxylase expression and increased Bcl-2/Bax ratio). Notably, CFX pretreatment also enhanced systemic and colon inflammation of dual-hit subjected mice. The exacerbated inflammatory response ran in tandem with a worsening of colonic architecture and gut microbiota perturbation. Finally, we demonstrated the beneficial effect of post-biotic sodium butyrate in limiting at once motor deficits, neuroinflammation, and colon damage and re-shaping microbiota composition in this novel dual-hit model of PD. Taken together, the bidirectional communication of the microbiota-gut-brain axis and the recapitulation of PD prodromal/pathogenic features make this new paradigm a useful tool for testing or repurposing new multi-target compounds in the treatment of PD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.