Urinary volatile metabolites of amygdala-kindled mice reveal novel biomarkers associated with temporal lobe epilepsy

Abstract

Abstract Epilepsy is a chronic neurological disorder affecting mammals, including humans. Uncontrolled epilepsy is associated with poor quality of life, accidents, and sudden death. In particular, temporal lobe epilepsy (TLE) is the most common type of pharmacoresistant epilepsy, which easily gets out of control in human adults. The aim of this study was to profile urinary volatile organic compounds (VOCs) in a mouse model of TLE using solid-phase microextraction (SPME) gas chromatography mass spectrometry (GC-MS). Thirteen urinary VOCs exhibited differential abundance between epileptic and control mice, and the corresponding areas under the receiver operating characteristic (ROC) curve were greater than 0.8. Principal component analysis (PCA) based on these 13 VOCs separated epileptic from sham operated-mice, suggesting that all these 13 VOCs are epilepsy biomarkers. Promax rotation and dendrogram analysis concordantly separated the 13 VOCs into three groups. Stepwise linear discriminant analysis extracted methanethiol; disulfide, dimethyl; and 2-butanone as predictors. Based on known metabolic systems, the results suggest that TLE induced by amygdala stimulation could affect both endogenous metabolites and the gut flora. Future work will elucidate the physiological meaning of the VOCs as end-products of metabolic networks and assess the impact of the metabolic background involved in development of TLE.