Integrative analysis of non-targeted lipidomic data and brain structural imaging identifies phosphatidylethanolamine ass
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ORIGINAL ARTICLE
Integrative analysis of non‑targeted lipidomic data and brain structural imaging identifies phosphatidylethanolamine associated with epileptogenesis Xiangmiao Qiu1 · Lu Zhang2 · Masako Kinoshita3 · Wanlin Lai1 · Wen Zheng2 · Anjiao Peng1 · Wanling Li1 · Linghui Yang4 · Lin Zhang1 · Meng Gong2 · Lei Chen1 Received: 11 March 2020 / Accepted: 25 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Introduction Epilepsy is a chronic disease, while epileptogenesis is a latent period where brain will be transformed into an epileptic one. Mechanisms of epileptogenesis remain unclear. Objectives We aim to provide information of hippocampal lipidomic changes related with epileptogenesis in two kindling models. Combining hippocampal structural imaging indices, our study also attempts to assess biochemical alterations as a function of epileptogenesis in a non-invasive way. Methods We constructed two kinds of chemical kindling models, which have long been used as models of epileptogenesis. Two kindling and one control groups were all subjected to structural imaging acquisition after successfully kindled. Voxel-based morphometry, a postprocessing method for brain imaging data, was used to segment and extract hippocampal gray matter volume for subsequent integrative analysis. LC–MS based lipidomic analysis was applied to identify distinct hippocampal lipidomic profiles between kindling and control groups. Further, we regress hippocampal structural indices on lipids to identify those associated with both epileptogenesis and brain structural changes. Results We report distinct lipidomic profiles between kindling groups and control. A total of 638 lipids were detected in all three groups. Among them were 98 individual lipids, showing significant alterations, in particular lipid class of phosphatidylethanolamine (PE), glucosylceramide and phosphatidylcholine. Hippocampal gray matter volumes were found significant different between groups (P = 0.0223). After combining brain imaging data, we demonstrate several individual PE, namely PE(O-18:1_22:3), PE(O-18:1_22:6) and PE(18:1_18:1), are associated with both epileptogenesis and hippocampal gray matter volume. Conclusion This study suggests metabolic pathway of PE might involve in epileptogenesis. Also, for the first time, we link level of PE with structural brain imaging indices, in an attempt to potentiate the futuristic application of noninvasive brain imaging techniques to identify epileptogenesis in its latent period. Keywords Epileptogenesis · Epilepsy · Lipidomics · Phosphatidylethanolamine
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11306-020-01731-w) contains supplementary material, which is available to authorized users. * Lei Chen [email protected] 1
Neurology Department, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu 610041, Sichuan, China
West China‑Washington Mitochondria and Metabolism Research Center, West China Hospita
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