Metabolomics using high-resolution magic angle spinning nuclear magnetic resonance: Neurotoxicological applications

Abstract

High-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) is a cutting-edge technology for metabolomics studies that has found application in pharmacology and toxicology. Metabolomics provides insight into how biological systems function, providing a unique chemical fingerprint of the physiological state of an organism. Using the high signal sensitivity and spectral resolution of HRMAS NMR, metabolic screening of intact tissue samples can be performed for complex organs such as the brain. In this study, we present a detailed HRMAS NMR methodology including sample preparation and experimental conditions to ensure data repeatability and reproducibility. We present the results of a neurotoxicology study, involving exposure of adult mice to 50 ppm of a legacy perfluoroalkyl substance, perfluorooctanoic acid (PFOA), through their drinking water for one month (n = 8/group). The PFOA exposed group had a significant increase in the relative concentration of glutamate compared to controls (p < 0.05), illustrating the potential for HRMAS NMR metabolomics to be used to determine the mode of action of neurotoxins and to provide an understanding of the molecular biochemical pathways impacted by toxicant exposure.