Abstract
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.
Highlights
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
Our results indicate that Glx (Glu/Gln) levels were consistently increased across the two brain regions in all age groups, after administration of valproic acid (VPA) and CPF compared to the control
Because of the genetic complexity of Autism spectrum disorders (ASD), there is currently no reliable biomarker that can be used to identify children at risk for ASD. The findings of this comprehensive study using an NMR spectroscopy-based metabolomics approach helped us to understand metabolic changes imposed by prenatal exposure to two chemical agents, VPA and CPF, which are associated with an increased risk of ASD occurrence, at different postnatal ages, in different brain tissues and in subjects of both sexes
Summary
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. By providing a global study of low molecular weight metabolites (
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