MicroRNA expression in the cuprizone-induced demyelination mouse model

Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). The neurotoxicant cuprizone (CPZ) has been extensively used to create a mouse model of demyelination. However, the changes of miRNA expression and effects on behavior of cuprizone treatment have not been clearly reported. We have analyzed the behavioral changes of mice given a diet containing 0.2% cuprizone for 6 weeks. To evaluate the changes of miRNA expression in CPZ-induced demyelination compared with control, we performed the Affymetrix GeneChip® miRNA 4.0 Array. We identified 1348 and 1253 differentially expressed miRNAs for control and CPZ-treated mice, respectively. Furthermore, the expression of 240 miRNAs was significantly changed in CPZ-induced mice comparing with control mice. These results suggest that the changes of miRNA expression in vivo may provide a new potential remyelination therapeutic target. We analyzed cerebellum from 2 subjects using Affymetrix GeneChip® miRNA 4.0 Array (Mus musculus) platform. Array data export processing and analysis were performed using Affymetrix® GeneChip Command Console® Software (AGCC).

中枢神经系统（CNS）脱髓鞘疾病中，髓鞘异常、少突胶质细胞损伤及伴随的胶质细胞激活现象十分常见。神经毒物双环己酮草酰二腙（cuprizone，CPZ）已被广泛应用于构建脱髓鞘小鼠模型。然而，目前关于双环己酮草酰二腙处理后微小RNA（miRNA）的表达变化及其对小鼠行为学的影响，尚未有明确的研究报道。本研究对喂食0.2%双环己酮草酰二腙饲料、持续6周的小鼠开展了行为学变化分析。为对比双环己酮草酰二腙诱导的脱髓鞘模型与对照组的miRNA表达差异，我们采用Affymetrix GeneChip® miRNA 4.0芯片进行了检测。我们分别在对照组与CPZ处理组小鼠中鉴定出1348个和1253个差异表达miRNA。进一步分析显示，与对照组相比，CPZ处理组小鼠中有240个miRNA的表达发生了显著改变。上述结果提示，体内miRNA的表达变化或许可为髓鞘再生治疗提供新的潜在靶点。我们采用Affymetrix GeneChip® miRNA 4.0芯片（Mus musculus，小家鼠）平台，对2只小鼠的小脑组织进行了分析。芯片数据的导出、处理与分析均通过Affymetrix® GeneChip Command Console®软件（AGCC）完成。