BACKGROUND Cuprizone administration in mice leads to oligodendrocyte death and demyelination. The effect is thought to reflect copper-chelation that leads to inhibition of complex IV of the mitochondrial respiratory chain. The effects this drug has on neurons are less well known. OBJECTIVE To investigate the toxic effects of cuprizone on mitochondria in neurons. METHODS Male c57Bl/6 mice were fed 0.2% cuprizone for up to 5 weeks. Cuprizone-fed and control mice were examined at week 1, 3, 5 and 4 weeks after cessation of cuprizone exposure. The brain was examined for myelin, complex I, complex IV and for COX/SDH activities. Mitochondrial-DNA was investigated for deletions and copy number variation. RESULTS We found decreased levels of complex IV in the cerebellar Purkinje neurons of mice exposed to cuprizone. This decrease was not related to a general decrease in mitochondrial volume or mass, as there were no differences in the levels of complex I or TOMM20. CONCLUSION Neurons are affected by cuprizone-treatment. Whether this mitochondrial dysfunction acts as a subclinical trigger for demyelination and the long-term axonal degeneration that proceeds after cuprizone treatment stops remains unclear.

中文翻译：

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在铜宗小鼠模型的神经元中，线粒体复合物 IV 丢失

背景在小鼠中施用Cuprizone导致少突胶质细胞死亡和脱髓鞘。该效应被认为反映了铜螯合导致线粒体呼吸链复合物 IV 的抑制。这种药物对神经元的影响鲜为人知。目的研究铜宗对神经元线粒体的毒性作用。方法 给雄性 c57Bl/6 小鼠喂食 0.2% 铜宗长达 5 周。在停止铜宗暴露后第 1、3、5 和 4 周检查铜宗喂养小鼠和对照小鼠。检查大脑的髓鞘、复合物 I、复合物 IV 和 COX/SDH 活性。研究了线粒体 DNA 的缺失和拷贝数变异。结果我们发现暴露于铜宗的小鼠小脑浦肯野神经元中复合物IV的水平降低。这种减少与线粒体体积或质量的普遍减少无关，因为复合物 I 或 TOMM20 的水平没有差异。结论 神经元受到铜宗治疗的影响。这种线粒体功能障碍是否是脱髓鞘和铜宗治疗停止后发生的长期轴突变性的亚临床触发因素尚不清楚。