1H NMR-BASED METABONOMICS IN BRAIN NUCLEUS ACCUMBENS AND STRIATUM FOLLOWING REPEATED COCAINE TREATMENT IN RATS
1H NMR-BASED METABONOMICS IN BRAIN NUCLEUS ACCUMBENS AND STRIATUM FOLLOWING REPEATED COCAINE TREATMENT IN RATS
复制标题
DOI：
10.1016/j.neuroscience.2012.05.019
复制
发表时间：
2012-08-30
期刊：
影响因子：
3.3
通讯作者：
Cen, X. -B.
中科院分区：
文献类型：
--
作者：
Li, Y.;Yan, G. -Y.;Cen, X. -B.
研究表明，可卡因会使大脑区域的一些脑代谢物发生改变；然而，对内源性代谢谱的研究一直较为缺乏。本研究采用基于离体氢 - 1核磁共振（H - 1 NMR）光谱的代谢组学方法，并结合偏最小二乘法，来探究接受可卡因处理的大鼠伏隔核（NAc）和纹状体中脑代谢物的变化。我们的研究结果显示，单次和重复给予可卡因均能诱导多种脑代谢物发生显著变化。在重复接受可卡因处理的大鼠的伏隔核和纹状体中，观察到神经递质谷氨酸和γ - 氨基丁酸（GABA）增加。重复给予可卡因后，伏隔核中的肌酸和牛磺酸增加，而纹状体中牛磺酸增加、肌酸减少。还观察到伏隔核和纹状体中N - 乙酰天冬氨酸升高，纹状体中乳酸降低，这可能反映了可卡因导致的线粒体功能失调；此外，伏隔核和纹状体中胆碱、磷酸胆碱和甘油的改变可能与膜损伤有关。而且，有条件性位置偏爱（CPP）装置和没有该装置的大鼠组在代谢物方面存在差异。总体而言，我们的研究结果首次提供了伏隔核和纹状体对可卡因反应的代谢组学特征证据，展现出区域特异性的改变模式。我们发现，重复给予可卡因会导致显著的代谢物改变，这些改变涉及大脑中的神经递质紊乱、氧化应激、线粒体功能失调和膜损伤。（C）2012国际脑研究组织。由爱思唯尔有限公司出版。保留所有权利。
Studies have shown a few cerebral metabolites modified by cocaine in brain regions; however, endogenous metabolic profiling has been lacking. Ex vivo H-1 NMR (hydrogen-1 nuclear magnetic resonance) spectroscopy-based metabonomic approach coupled with partial least squares was applied to investigate the changes of cerebral metabolites in nucleus accumbens (NAc) and striatum of rats subjected to cocaine treatment. Our results showed that both single and repeated cocaine treatment can induce significant changes in a couple of cerebral metabolites. The increase of neurotransmitters glutamate and gamma-amino butyric acid (GABA) were observed in NAc and striatum from the rats repeatedly treated with cocaine. Creatine and taurine increased in NAc whereas taurine increased and creatine decreased in striatum after repeated cocaine treatment. Elevation of N-acetylaspartate in NAc and striatum and decrease of lactate in striatum were observed, which may reflect the mitochondria dysregulation caused by cocaine; moreover, alterations of choline, phosphocholine and glycerol in NAc and striatum could be related to membrane disruption. Moreover, groups of rats with and without conditioned place preference (CPP) apparatus are presenting difference in metabolites. Collectively, our results provide the first evidence of metabonomic profiling of NAc and striatum in response to cocaine, exhibiting a regionally-specific alteration patterns. We find that repeated cocaine administration leads to significant metabolite alterations, which are involved in neurotransmitter disturbance, oxidative stress, mitochondria dysregulation and membrane disruption in brain. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.