Metabolic Disturbances in the Gut-brain Axis of a Mouse Model of MPTP-induced Parkinsonism Evaluated by Nuclear Magnetic Resonance

• Published in: Neuroscience Vol. 526; pp. 21 - 34
• Main Authors: Pedro Amorim Neto, Dionísio, Vitor Pereira de Godoy, João, Tostes, Katiane, Pelegrini Bosque, Beatriz, Vieira Rodrigues, Paulla, Aparecida Rocco, Silvana, Luis Sforça, Mauricio, de Castro Fonseca, Matheus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 21.08.2023
• Subjects: gut-brain axis; metabolome; neurodegenerative diseases; nuclear magnetic resonance; Parkinson’s disease; neurodegenerative diseases; PD; 1H NMR; αSyn; nuclear magnetic resonance; metabolome; Parkinson’s disease; gut-brain axis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2023.06.010

[Display omitted] •The gut-microbiota-brain axis has a role in the physiological basis of neurodegeneration.•Parkinson’s disease frequently leads to gastrointestinal disfunction.•MPTP-induced parkinsonism leads to metabolic changes in the gut-microbiota-brain-axis.•NMR-based metabolomics represent an alternative strategy for the identification of biomarkers. Parkinson's Disease is a synucleinopathy that primarily affects the dopaminergic cells of the central nervous system, leading to motor and gastrointestinal disturbances. However, intestinal peripheral neurons undergo a similar neurodegeneration process, marked by α-synuclein (αSyn) accumulation and loss of mitochondrial homeostasis. We investigated the metabolic alterations in different biometrics that compose the gut-brain axis (blood, brain, large intestine, and feces) in an MPTP-induced mouse model of sporadic Parkinson's Disease. Animals received escalating administration of MPTP. Tissues and fecal pellets were collected, and the metabolites were identified through the untargeted Nuclear Magnetic Resonance spectroscopic (1H NMR) technique. We found differences in many metabolites from all the tissues evaluated. The differential expression of metabolites in these samples mainly reflects inflammatory aspects, cytotoxicity, and mitochondrial impairment (oxidative stress and energy metabolism) in the animal model used. The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. This data reinforces previous studies showing that Parkinson’s disease is associated with metabolic perturbation not only in brain-related tissues, but also in periphery structures such as the gut. In addition, the evaluation of the microbiome and metabolites from gut and feces emerge as promising sources of information for understanding the evolution and progression of sporadic Parkinson's Disease.