Abstract：
Dietary administration of a copper chelator, cuprizone (CPZ), has long been reported to induce intense and reproducible demyelination of several brain structures such as the corpus callosum. Despite the widespread use of CPZ as an animal model for demyelinating diseases such as multiple sclerosis (MS), the mechanism by which it induces demyelination and then allows robust remyelination is still unclear. An intensive mapping of the cell dynamics of oligodendrocyte (OL) lineage during the de- and remyelination course would be particularly important for a deeper understanding of this model. Here, using a panel of OL lineage cell markers as in situ hybridization (ISH) probes, including Pdgfra, Plp, Mbp, Mog, Enpp6, combined with immunofluorescence staining of CC1, SOX10, we provide a detailed dynamic profile of OL lineage cells during the entire course of the model from 1, 2, 3.5 days, 1, 2, 3, 4,5 weeks of CPZ treatment, as well as after 1, 2, 3, 4 weeks of recovery from CPZ treatment. The result showed an unexpected early death of mature OLs and response of OL progenitor cells (OPCs) in vivo upon CPZ challenge, and a prolonged upregulation of myelin-forming OLs compared to the intact control even 4 weeks after CPZ withdrawal. These data may serve as a basic reference system for future studies of the effects of any intervention on de- and remyelination using the CPZ model, and imply the need to optimize the timing windows for the introduction of pro-remyelination therapies in demyelinating diseases such as MS.
摘要：
铜螯合剂的饮食管理，铜宗（CPZ），长期以来，据报道会引起几种大脑结构（例如call体）强烈且可重复的脱髓鞘。尽管广泛使用CPZ作为脱髓鞘疾病如多发性硬化症（MS）的动物模型，其诱导脱髓鞘,然后进行强力髓鞘再生的机制尚不清楚.在去髓鞘再生过程中，少突胶质细胞（OL）谱系的细胞动力学的密集映射对于更深入地了解该模型尤为重要。这里,使用一组OL谱系细胞标记作为原位杂交（ISH）探针，包括pdgfra,Plp,Mbp,Mog,Enpp6，结合CC1，SOX10的免疫荧光染色，我们在模型的整个过程中从1、2、3.5天提供了OL谱系细胞的详细动态概况，CPZ治疗1、2、3、4、5周，以及从CPZ治疗恢复1、2、3、4周后。结果表明，在CPZ攻击后，体内成熟的OLs和OL祖细胞（OPCs）的反应出乎意料的早期死亡。与完整对照相比，即使在CPZ戒断后4周，髓鞘形成性OL的上调也延长。这些数据可以作为一个基本的参考系统，用于将来研究任何干预对使用CPZ模型的去髓鞘和髓鞘再生的影响。并暗示需要优化时间窗口，以在脱髓鞘疾病如MS中引入髓鞘再生疗法。
