National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, 28# Gaopeng Avenue, High Technological Development Zone, Chengdu 610041, China.
BMC Neurosci. 2014 Feb 22;15:32. doi: 10.1186/1471-2202-15-32.
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.
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.
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.
尼古丁从香烟烟雾中被迅速吸收，因此随着烟草制品的广泛使用，会引发许多慢性疾病。研究表明，尼古丁会修饰一些大脑代谢物；然而，大脑内源性代谢组学尚未得到充分探索。
我们应用基于核磁共振的代谢组学方法来研究大脑海马体、伏隔核（NAc）、前额叶皮层（PFC）和纹状体的内源性代谢组学特征。我们发现尼古丁显著增加了小鼠的 CPP 值，并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变化。这些修饰的代谢物包括谷氨酸、乙酰胆碱、色胺、葡萄糖、乳酸、肌酸、3-羟丁酸和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，尼古丁还显著修饰了海马体和纹状体中的谷胱甘肽和牛磺酸、PFC 中的磷酸胆碱和 NAc 中的甘油，提示抗氧化应激反应和膜代谢的失调。
尼古丁在大脑中引起了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。
