Aterosklerotik doz TMAO, Parkinson hastalığının MPTP fare modelinde redoks dengesizliklerini ve motor disfonksiyonlarını vurgular.

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Parkinson's Disease (PD) involves the loss of dopaminergic neurons and the formation of Lewy bodies consisting of alpha-synuclein (αSin) aggregates. Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, has emerged as a molecule of interest due to pro-inflammatory, pro-oxidative, and neurodegenerative effects. We aim to assess whether lower doses of TMAO (40 mg/kg bw, gavage, once daily, day 0-42), as those used in atherosclerosis experimental models, can exacerbate oxidative stress, neuroinflammation, motor dysfunction, and neurodegeneration in a semi-acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD model (30 mg/kg bw MPTP, intraperitoneal, once daily, day 20-24). Motor behavioral testing functionally validated the model, with MPTP impairing performance across Rotarod latency time (p p p p p p p p p p > 0.05), whereas NF-κB p65 was paradoxically increased only in the TMAO (p p p p p p p p < 0.01 vs. MPTP). These findings carry clinical relevance in the context of Parkinson's disease, suggesting that gut microbiome-derived metabolites may represent a pathological connection capable of increasing both cardiovascular risk and the progression of neurodegenerative disorders.

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