Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
Division of Bio-Medical Science & Technology, KIST School, Korea National University of Science and Technology (UST), Seoul, Republic of Korea.
Commun Biol. 2024 Nov 30;7(1):1599. doi: 10.1038/s42003-024-07207-0.
Acute dependence to nicotine can rapidly elicit withdrawal symptoms. However, protracted withdrawal signs from acute nicotine dependence have not been explored. Here, we demonstrate that acute nicotine dependence induces delayed neurobehavioral defects in mice. Acute nicotine dependence led to impairment in passive avoidance but without changes in innate anxiety or learning/memory. Concurrently, F-actin level in the dorsal striatum was aberrantly increased, striatal dendritic spine density was reduced, and striatal neural population activity was diminished after acute nicotine dependence. The smoking-related and synapse-associated microRNA miR-27b was decreased in the dorsal striatum throughout the protracted phase of acute nicotine dependence. In silico analysis with empirical validation revealed the neuronal membrane-associated gene Marcks as a direct inhibition target of miR-27b, and that striatal Marcks was aberrantly enhanced after acute nicotine dependence. Our data collectively indicate that acute nicotine dependence accompanies a series of protracted neurobehavioral sequelae with striatal structural, electrophysiological, and molecular dysfunctions.
急性尼古丁依赖会迅速引起戒断症状。然而，急性尼古丁依赖引起的长期戒断迹象尚未得到探索。在这里，我们证明急性尼古丁依赖会导致小鼠出现延迟性神经行为缺陷。急性尼古丁依赖导致被动回避受损，但先天焦虑或学习/记忆没有变化。同时，急性尼古丁依赖后背侧纹状体中的 F-肌动蛋白水平异常升高，纹状体树突棘密度降低，纹状体神经元群体活性降低。与吸烟相关的突触相关 microRNA miR-27b 在急性尼古丁依赖的整个迁延期均减少。通过经验验证的计算机分析显示，神经元膜相关基因 Marcks 是 miR-27b 的直接抑制靶标，急性尼古丁依赖后纹状体 Marcks 异常增强。我们的数据共同表明，急性尼古丁依赖伴随着一系列与纹状体结构、电生理和分子功能障碍相关的迁延性神经行为后遗症。
