MS-Based Metabolomics for the Investigation of Neuro-Metabolic Changes Associated with BDE-47 Exposure in C57BL/6 Mice

Polybrominated diphenyl ethers (PBDE), as one kind of the major persistent organic pollutants (POP), have potential adverse effects on human health. 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) has been identified as one of the dominant PBDE congener in environmental and human samples. In this paper, liquid chromatography–orbitrap mass spectrometry (LC-Orbitrap MS) was applied for the profiling analysis of small metabolites in mice serum and striatum. The metabolic characteristics of adult male C57BL/6 mice exposed to BDE-47 were investigated with a non-targeted metabolomics method. The partial least-squares discriminant analysis (PLS-DA) indicated that the metabolites profile was significantly changed due to the exposure. Fifty-seven differential metabolites that significantly altered in mice serum and striatum were identified through databases searching and authentic standards confirmation. The related metabolic pathways mainly involved purine metabolism, alanine, aspartate and glutamate metabolism, tryptophan metabolism, phenylalanine metabolism, and glutathione metabolism. On the basis of metabolic variations, molecular mechanisms including disturbance of dopaminergic system, neurotransmitters regulation, DNA methylation, and oxidative stress were proposed. The obtained results suggested that LC-Orbitrap MS-based metabolomics had the great potential for molecular understanding of metabolic regulation linked to the exposure of environment pollutants.