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

Author(s)

Amorim Neto, Dionisio Pedro ; de Godoy, Joao Vitor Pereira ; Tostes, Katiane ; Bosque, Beatriz Pelegrini ; Rodrigues, Paulla Vieira ; Rocco, Silvana Aparecida ; Sforca, Mauricio Luis ; Fonseca, Matheus de Castro

• Document type: Journal article
• Source: Neuroscience; v. 526, p. 14-pg., 2023-06-27.

Abstract

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 a-synuclein (aSyn) 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.& COPY; 2023 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 19/24511-0 - The role of LRRK2 and Rab GTPases in the neurodegeneration during sporadic Parkinson's Disease
• Grantee: Beatriz Pelegrini Bosque
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/20014-0 - The gut-brain connection: role of the gut microbioma in the outcome and development of the sporadic Parkinson's disease
• Grantee: Matheus de Castro Fonseca
• Support Opportunities: Regular Research Grants