1H-Nuclear magnetic resonance-based metabolomic analysis of brain in mice with nicotine treatment
1H-Nuclear magnetic resonance-based metabolomic analysis of brain in mice with nicotine treatment
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DOI：
10.1186/1471-2202-15-32
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发表时间：
2014-02-22
期刊：
影响因子：
2.4
通讯作者：
Cen, Xiaobo
中科院分区：
文献类型：
--
作者：
Li, Hongyu;Chen, Bo;Cen, Xiaobo
背景：尼古丁可从香烟烟雾中快速吸收，因此随着烟草制品的广泛使用，会引发多种慢性疾病。已有研究表明尼古丁会改变一些大脑代谢物；然而，大脑内源性代谢谱尚未得到充分研究。
结果：基于核磁共振氢谱（¹H NMR）的代谢组学方法被用于研究大脑海马体、伏隔核（NAc）、前额叶皮质（PFC）和纹状体的内源性代谢谱。我们发现尼古丁显著增加了小鼠的条件性位置偏爱（CPP），且在尼古丁处理的小鼠中，一些特定的大脑代谢物发生了差异性变化。这些改变的代谢物包括谷氨酸、乙酰胆碱、色胺、葡萄糖、乳酸、肌酸、3 - 羟基丁酸以及烟酰胺腺嘌呤二核苷酸（NAD），它们与神经递质和能量来源密切相关。此外，海马体和纹状体中的谷胱甘肽与牛磺酸、前额叶皮质中的磷酸胆碱以及伏隔核中的甘油受尼古丁影响显著，这意味着抗氧化应激反应和膜代谢的失调。
结论：尼古丁会在大脑中诱导显著的代谢组学改变，涉及神经递质紊乱、能量代谢失调、抗氧化和膜功能破坏，以及氨基酸代谢失衡。这些发现为尼古丁的奖赏效应及其潜在机制提供了新的见解。
Background: Nicotine is rapidly absorbed from cigarette smoke and therefore induces a number of chronic illnesses with the widespread use of tobacco products. Studies have shown a few cerebral metabolites modified by nicotine; however, endogenous metabolic profiling in brain has not been well explored.Results: H NMR-based on metabonomics was applied to investigate the endogenous metabolic profiling of brain hippocampus, nucleus acumens (NAc), prefrontal cortex (PFC) and striatum. We found that nicotine significantly increased CPP in mice, and some specific cerebral metabolites differentially changed in nicotine-treated mice. These modified metabolites included glutamate, acetylcholine, tryptamine, glucose, lactate, creatine, 3-hydroxybutyrate and nicotinamide-adenine dinucleotide (NAD), which was closely associated with neurotransmitter and energy source. Additionally, glutathione and taurine in hippocampus and striatum, phosphocholine in PFC and glycerol in NAc were significantly modified by nicotine, implying the dysregulation of anti-oxidative stress response and membrane metabolism.Conclusions: Nicotine induces significant metabonomic alterations in brain, which are involved in neurotransmitter disturbance, energy metabolism dysregulation, anti-oxidation and membrane function disruptions, as well as amino acid metabolism imbalance. These findings provide a new insight into rewarding effects of nicotine and the underlying mechanism.