Repeated exposure of cocaine alters mitochondrial dynamics in mouse neuroblastoma Neuro2a
Repeated exposure of cocaine alters mitochondrial dynamics in mouse neuroblastoma Neuro2a
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DOI：
10.1016/j.neuro.2019.09.001
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发表时间：
2019-12-01
期刊：
影响因子：
3.4
通讯作者：
Uemura, Koichi
中科院分区：
文献类型：
--
作者：
Funakoshi, Takeshi;Furukawa, Mako;Uemura, Koichi
长期滥用精神活性药物（包括可卡因）会通过改变神经元可塑性而导致成瘾、依赖和脑部疾病。线粒体的分裂和融合，统称为线粒体动力学，不仅参与维持神经元的稳态，而且参与神经元回路的重组。本研究的目的是研究直接和重复接触可卡因对体外神经元细胞线粒体动力学的影响。Neuro 2a小鼠神经母细胞瘤细胞反复暴露于600 μ M可卡因（每周2次至3次）3周，导致线粒体跨膜电位降低，自噬激活，以及参与线粒体自噬的蛋白质Parkin上调。线粒体分裂基因的表达增加，并在丝氨酸-616磷酸化的DRP 1，线粒体分裂的关键调节器，显着增加，观察到细胞反复暴露于600 μ M可卡因。电子显微镜显示可卡因处理的细胞中的线粒体的数量显着增加与对照细胞相比。因此，我们的研究结果表明，重复可卡因暴露不仅会导致线粒体功能障碍，而且会改变Neuro 2a细胞中的线粒体动力学。线粒体动力学的变化可能参与可卡因重复暴露期间的神经适应。
Chronic abuse of psychoactive drugs including cocaine causes addiction, dependence, and brain disorders through the alteration of neuronal plasticity. Mitochondria] fission and fusion, collectively called as mitochondrial dynamics, participates in not only the maintenance of neuronal homeostasis but also reorganization of neuronal circuits. The purpose of this study is to examine effects of direct and repeated exposure of cocaine on mitochondrial dynamics in neuronal cells in vitro. Repeated exposure to 600 mu M cocaine (2 similar to 3 times per week) of Neuro2a mouse neuroblastoma cells for 3 weeks resulted in decrease of mitochondrial transmembrane potential, activation of autophagy, and upregulation of Parkin, a protein involved in mitochondrial autophagy. Increased expression of mitochondrial fission genes and significant increase in the ser-616 phosphorylated-DRP1, the key regulator of mitochondrial fission, were observed in the cells exposed repeatedly to 600 mu M cocaine. Electron microscopy showed significant increase in the number of mitochondria in cocaine-treated cells compared with control cells. Thus, our results show that repeated cocaine exposure not only causes mitochondrial dysfunction but also alters mitochondrial dynamics in Neuro2a cells. Changes in the mitochondrial dynamics might be involved in neural adaptation during repeated cocaine exposure.