Open AccessNMR-Based Metabolomics Approach to Explore Brain Metabolic Changes Induced by Prenatal Exposure to Autism-Inducing Chemicals
Author(s) -
Ana Cristina Abreu,
Miguel Morales Navas,
Cristian Perez Fernández,
Fernando Sánchez-Santed,
Ignacio Fernández
Publication year - 2021
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.1c00053
Subject(s) - metabolomics , metabolite , glutamine , autism , choline , biology , taurine , betaine , glutamate receptor , valproic acid , biochemistry , amino acid , pharmacology , medicine , neuroscience , bioinformatics , epilepsy , psychiatry , receptor
NMR offers the unique potential to holistically screen hundreds of metabolites and has already proved to be a powerful technique able to provide a global picture of a wide range of metabolic processes underlying complex and multifactorial diseases, such as neurodegenerative and neurodevelopmental diseases. The aim of this study was to apply an NMR-based metabolomics approach to explore brain metabolic changes in both male and female rats induced by prenatal exposure to two chemicals associated with autism disorders-the organophosphorus pesticide chlorpyrifos (CPF) and the antiepileptic drug valproic acid (VPA)-at different postnatal ages. Depending on the age and on the brain region (hippocampus and cerebellum), several metabolites were shown to be significantly affected by exposure to both compounds. The evaluation of the spectral profiles revealed that the nervous-system-specific metabolite N -acetylaspartate (NAA), amino acid neurotransmitters (e.g., glutamate, glutamine, GABA, glycine), pyroglutamic acid, unsaturated fatty acids, and choline-based compounds are discriminant biomarkers. Additionally, metabolic changes varied as a function of age, but importantly not of sex.