Lin Ming, Xu Jiamin, Liu Xi, Dai Zhenfeng, Liu Zhimin, Zhao Xin, Sun Yi, Pu Xiaoping
National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University Beijing 100191 China
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Beijing 100191 China.
RSC Adv. 2019 Dec 12;9(70):41107-41119. doi: 10.1039/c9ra08096a. eCollection 2019 Dec 9.
Methamphetamine (METH) has already been a serious problem all over the world. The identification of related biomarkers and pathways is helpful to evaluate the degree of METH addiction, develop appropriate treatment during abstinence, and explore the mechanism. Here, it is the first time to perform metabolomics profiling of METH addicted human serum and three regions of METH-induced conditioned place preference (CPP) rat brain by using UHPLC-MS/MS and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), respectively. Untargeted metabolomics analysis demonstrated clear differences between METH abusers and the healthy control by finding 35 distinct expressed metabolites in serum, including 5 TCA intermediates, 17 amino acids and 13 other biomolecules, 15 of which were newly identified following METH exposure. By using MALDI-MSI, the relative quantification and distribution of 14 metabolites were investigated in the nucleus accumbens (NAc), dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) of CPP rat brain. Taken together, METH addiction could influence energy metabolism, amino acids metabolism, and phospholipids metabolism. A multi-parameter model consisting of these related metabolites can be established as a METH addiction biomarker in the future. The mapping of phospholipids provided new insights into the mechanism of METH addiction. Notably, the trend of metabolite changes in NAc and dHPC was almost the same, while it was opposite between dHPC and vHPC. It seems that NAc and dHPC were the two regions more susceptible to METH administration in the brain. And dHPC and vHPC play different roles in METH addiction proved by metabolites mapping.
甲基苯丙胺（METH）已成为全球范围内的一个严重问题。识别相关生物标志物和途径有助于评估METH成瘾程度、在戒断期间制定适当的治疗方案以及探索其机制。在此，首次分别使用超高效液相色谱-串联质谱（UHPLC-MS/MS）和基质辅助激光解吸/电离质谱成像（MALDI-MSI）对METH成瘾者的血清以及METH诱导的条件性位置偏爱（CPP）大鼠脑的三个区域进行代谢组学分析。非靶向代谢组学分析表明，METH滥用者与健康对照之间存在明显差异，在血清中发现了35种差异表达的代谢物，包括5种三羧酸循环中间体、17种氨基酸和13种其他生物分子，其中15种是METH暴露后新鉴定出的。通过MALDI-MSI，研究了CPP大鼠脑伏隔核（NAc）、背侧海马（dHPC）和腹侧海马（vHPC）中14种代谢物的相对定量和分布。综上所述，METH成瘾可影响能量代谢、氨基酸代谢和磷脂代谢。未来可以建立一个由这些相关代谢物组成的多参数模型作为METH成瘾的生物标志物。磷脂图谱为METH成瘾机制提供了新的见解。值得注意的是，NAc和dHPC中代谢物变化趋势几乎相同，而dHPC和vHPC之间则相反。似乎NAc和dHPC是大脑中对METH给药更敏感的两个区域。代谢物图谱证明dHPC和vHPC在METH成瘾中发挥不同作用。
