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

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.

SUBMITTER: Fujita A

PROVIDER: S-EPMC6646363 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Fujita Akiko A Ota Manami M Kato Keiko K

Scientific reports 20190722 1

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 spectromet ...[more]

PMID: 31332211

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Project description:PurposeIdentifying relationships between clinical features and quantitative characteristics of the amygdala-hippocampal and thalamic subregions in mesial temporal lobe epilepsy (mTLE) may offer insights into pathophysiology and the basis for imaging prognostic markers of treatment outcome. Our aim was to ascertain different patterns of atrophy or hypertrophy in mesial temporal sclerosis (MTS) patients and their associations with post-surgical seizure outcomes. To assess this aim, this study is designed in 2 folds: (1) hemispheric changes within MTS group and (2) association with postsurgical seizure outcomes.Methods and materials27 mTLE subjects with mesial temporal sclerosis (MTS) were scanned for conventional 3D T1w MPRAGE images and T2w scans. With respect to 12 months post-surgical seizure outcomes, 15 subjects reported being seizure free (SF) and 12 reported continued seizures. Quantitative automated segmentation and cortical parcellation were performed using Freesurfer. Automatic labeling and volume estimation of hippocampal subfields, amygdala, and thalamic subnuclei were also performed. The volume ratio (VR) for each label was computed and compared between (1) between contralateral and ipsilateral MTS using Wilcoxon rank-sum test and (2) SF and not seizure free (NSF) groups using linear regression analysis. False Discovery rate (FDR) with significant level of 0.05 were used in both analyses to correct for multiple comparisons.ResultsAmygdala: The medial nucleus of the amygdala was the most significantly reduced in patients with continued seizures when compared to patients who remained seizure free. Hippocampus: Comparison of ipsilateral and contralateral volumes with seizure outcomes showed volume loss was most evident in the mesial hippocampal regions such as CA4 and hippocampal fissure. Volume loss was also most explicit in the presubiculum body in patients with continued seizures at the time of their follow-up. Ipsilateral MTS compared to contralateral MTS analysis showed the heads of the ipsilateral subiculum, presubiculum, parasubiculum, dentate gyrus, CA4, and CA3 were more significantly affected than their respective bodies. Volume loss was most noted in mesial hippocampal regions. Thalamus: VPL and PuL were the most significantly reduced thalamic nuclei in NSF patients. In all statistically significant areas, volume reduction was observed in the NSF group. No significant volume reductions were noted in the thalamus and amygdala when comparing ipsilateral to contralateral sides in mTLE subjects.ConclusionsVarying degrees of volume loss were demonstrated in the hippocampus, thalamus, and amygdala subregions of MTS, especially between patients who remained seizure-free and those who did not. The results obtained can be used to further understand mTLE pathophysiology.Clinical relevance/applicationIn the future, we hope these results can be used to deepen the understanding of mTLE pathophysiology, leading to improved patient outcomes and treatments.

Dataset Information

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

Publications

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

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