Nicotine induces morphological and functional changes in astrocytes via nicotinic receptor activity.
Nicotine induces morphological and functional changes in astrocytes via nicotinic receptor activity.
复制标题
尼古丁通过烟碱受体活性诱导星形胶质细胞的形态和功能变化。
作者：
Aryal SP;Fu X;Sandin JN;Neupane KR;Lakes JE;Grady ME;Richards CI
尼古丁是一种存在于烟草中的高度成瘾性化合物，它会导致大脑不同区域释放多巴胺。最近的研究表明，星形胶质细胞表达烟碱乙酰胆碱受体（nAChRs）和介导的钙信号。在这项研究中，我们研究了由于尼古丁暴露的星形胶质细胞的形态和功能适应。利用荧光和原子力显微镜相结合，我们表明，尼古丁处理的星形胶质细胞表现出时间依赖性的近端和精细过程的数量和长度的重塑。用拮抗剂阻断nAChR活性完全消除了尼古丁对星形胶质细胞形态的影响，表明尼古丁的作用是由这些受体介导的。功能研究表明，24小时尼古丁处理诱导细胞索马和突起中更高水平的钙活性，在突起中观察到更实质性的变化。通过细胞因子释放和GFAP表达确定，尼古丁即使在高浓度（10 μM）下也不会诱导反应性星形胶质细胞增多。我们设计了组织清除实验，以测试是否在小鼠中使用星形胶质细胞特异性Aldh 1 l1-tdTomato敲除在体内发生形态学变化。我们发现，尼古丁诱导前额叶皮层，海马CA 1区和黑质的星形胶质细胞的体积的变化。这些结果表明，尼古丁直接改变了星形胶质细胞的功能和形态学特性，可能导致尼古丁滥用的潜在机制。
Nicotine is a highly addictive compound present in tobacco, which causes the release of dopamine in different regions of the brain. Recent studies have shown that astrocytes express nicotinic acetylcholine receptors (nAChRs) and mediate calcium signaling. In this study we examine the morphological and functional adaptations of astrocytes due to nicotine exposure. Utilizing a combination of fluorescence and atomic force microscopy, we show that nicotine treated astrocytes exhibit time dependent remodeling in the number and length of both proximal and fine processes. Blocking nAChR activity with an antagonist completely abolishes nicotine’s influence on astrocyte morphology indicating that nicotine’s action is mediated by these receptors. Functional studies show that 24-hour nicotine treatment induces higher levels of calcium activity in both the cell soma and the processes with a more substantial change observed in the processes. Nicotine does not induce reactive astrocytosis even at high concentrations (10 μM) as determined by cytokine release and GFAP expression. We designed tissue clearing experiments to test whether morphological changes occur in vivo using astrocyte specific Aldh1l1-tdTomato knock in mice. We find that nicotine induces a change in the volume of astrocytes in the prefrontal cortex, CA1 of the hippocampus, and the substantia nigra. These results indicate that nicotine directly alters the functional and morphological properties of astrocytes potentially contributing to the underlying mechanism of nicotine abuse.
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