Zhu Beibei, Li Xiangyu, Chen Huan, Wang Hongjuan, Zhu Xinchao, Hou Hongwei, Hu Qingyuan
China National Tobacco Quality Supervision and Test Center, Zhengzhou, 450001, China.
China National Tobacco Quality Supervision and Test Center, Zhengzhou, 450001, China.
Biochem Biophys Res Commun. 2017 May 13;486(4):971-977. doi: 10.1016/j.bbrc.2017.03.141. Epub 2017 Mar 28.
Repeated exposures to nicotine are known to result in persistent changes in proteins expression in addiction-related brain regions, such as the striatum, nucleus accumbens and prefrontal cortex, but the changes induced in the protein content of the hippocampus remain poorly studied. This study established a rat model of nicotine-induced conditioned place preference (CPP), and screened for proteins that were differentially expressed in the hippocampus of these rats using isobaric tags for relative and absolute quantitation labeling (iTRAQ) coupled with 2D-LC MS/MS. The nicotine-induced CPP was established by subcutaneously injecting rats with 0.2 mg/kg nicotine. Relative to the control (saline) group, the nicotine group showed 0.67- and 1.5-fold changes in 117 and 10 hippocampal proteins, respectively. These differentially expressed proteins are mainly involved in calcium-mediated signaling, neurotransmitter transport, GABAergic synapse function, long-term synaptic potentiation and nervous system development. Furthermore, RT-PCR was used to confirmed the results of the proteomic analysis. Our findings identify several proteins and cellular signaling pathways potentially involved in the molecular mechanisms in the hippocampus that underlie nicotine addiction. These results provide insights into the mechanisms of nicotine treatment in hippocampus.
已知反复接触尼古丁会导致成瘾相关脑区（如纹状体、伏隔核和前额叶皮质）的蛋白质表达持续变化，但对海马体蛋白质含量的诱导变化仍研究不足。本研究建立了尼古丁诱导的条件性位置偏爱（CPP）大鼠模型，并使用相对和绝对定量标记的等压标签（iTRAQ）结合二维液相色谱串联质谱（2D-LC MS/MS）筛选这些大鼠海马体中差异表达的蛋白质。通过给大鼠皮下注射0.2mg/kg尼古丁建立尼古丁诱导的CPP。相对于对照组（生理盐水），尼古丁组在117种和10种海马体蛋白质中分别出现了0.67倍和1.5倍的变化。这些差异表达的蛋白质主要参与钙介导的信号传导、神经递质转运、γ-氨基丁酸能突触功能、长期突触增强和神经系统发育。此外，使用逆转录聚合酶链反应（RT-PCR）来证实蛋白质组学分析的结果。我们的研究结果确定了几种可能参与海马体中尼古丁成瘾分子机制的蛋白质和细胞信号通路。这些结果为海马体中尼古丁治疗的机制提供了见解。
