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杏仁核点燃模型小鼠尿液中的挥发性代谢物揭示了与颞叶癫痫相关的新型生物标志物。

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

机构信息

Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-ku, Kyoto, Japan.

出版信息

Sci Rep. 2019 Jul 22;9(1):10586. doi: 10.1038/s41598-019-46373-8.

DOI:10.1038/s41598-019-46373-8
PMID:31332211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6646363/
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.

摘要

癫痫是一种影响哺乳动物(包括人类)的慢性神经障碍。不受控制的癫痫与生活质量差、事故和突然死亡有关。特别是颞叶癫痫(TLE)是最常见的耐药性癫痫类型,容易在成年人类中失控。本研究的目的是使用固相微萃取(SPME)气相色谱-质谱(GC-MS)对 TLE 小鼠模型中的尿挥发性有机化合物(VOC)进行分析。13 种尿 VOC 在癫痫和对照小鼠之间表现出差异丰度,相应的接收器操作特性(ROC)曲线下面积大于 0.8。基于这 13 种 VOC 的主成分分析(PCA)将癫痫与假手术小鼠分开,表明所有这些 VOC 都是癫痫生物标志物。Promax 旋转和聚类分析将这 13 种 VOC 分为三组。逐步线性判别分析提取甲硫醇、二硫化二甲基和 2-丁酮作为预测因子。根据已知的代谢系统,结果表明,杏仁核刺激引起的 TLE 可能会影响内源性代谢物和肠道菌群。未来的工作将阐明 VOC 作为代谢网络终产物的生理意义,并评估参与 TLE 发展的代谢背景的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/49d37d09d857/41598_2019_46373_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/7482f71dd8dd/41598_2019_46373_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/3c7e21bb0453/41598_2019_46373_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/bee7f70f6702/41598_2019_46373_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/ae6d58a5626f/41598_2019_46373_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/49d37d09d857/41598_2019_46373_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/7482f71dd8dd/41598_2019_46373_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/3c7e21bb0453/41598_2019_46373_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/bee7f70f6702/41598_2019_46373_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/ae6d58a5626f/41598_2019_46373_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bb2/6646363/49d37d09d857/41598_2019_46373_Fig5_HTML.jpg

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