少突胶质前体细胞特异性miR-124在中枢神经系统炎性脱髓鞘疾病中的作用机制研究

中枢神经系统炎性脱髓鞘疾病（如多发硬化）是造成青壮年神经系统功能性残障的重要因素。以促进髓鞘再生为目标的神经保护修复治疗是该类疾病免疫调节治疗之外的极具潜力的治疗方向。我们前期研究发现miR-124在实验性自身反应性脑脊髓炎（EAE，多发硬化症动物模型）动物脑和脊髓中表达显著下调，初步证实其可能通过调控髓鞘再生参与疾病进程。因此，本研究拟利用实时定量PCR，荧光原位杂交等技术深入分析miR-124在EAE中的时空和细胞差异表达特征。结合体内和体外手段，通过观察少突胶质前体细胞（OPC）特异性敲除或过表达miR-124，研究OPC特异性miR-124对EAE疾病进程的影响，并进一步结合生物信息学和遗传学技术确证OPC中miR-124影响EAE疾病进程的直接作用靶点并阐明其作用机制。研究结果可望为中枢神经系统炎性脱髓鞘疾病的神经保护和修复治疗提供新的治疗靶点和治疗手段。

Central nernous system (CNS) inflammatory demyelinating diseases (e.g. multiple sclerosis, MS) are the major reasons to cause CNS disability in young adults. Neuroprotective and repair therapy by promoting remyelination will have great potential to treat these diseases in conjunction with disease-modifying medications. Experimental autoimmune encephalomyelitis (EAE) is the animal model of multiple sclerosis. Previously we found that miR-124 was significantly down-regulated in the brain and spinal cord of EAE mice. In addition, the preliminary data suggested that miR-124 may impact EAE by regulating the processes of demyelination and remyelination. Based on these results, we will use real-time PCR and FISH methods to furtherly characterize the spatiotemporal and cell-specific expression of miR-124 in EAE mice. Then by oligodendrocyte progenitor cell-specific silencing or overexpression of miR-124 in both in vitro cultured OPCs and in vivo animal models, we will try to identify the role of OPC-restricted miR-124 in affecting the disease progression.In addition, bininformatic- and gentic-techniques will be used to screen and confirm the direct targets of miR-124 and uncover how this miRNA modulate EAE pathogenesis through promoting remyelination. This project will help us identifying potential novel drugs to promote remyelination to treat multiple sclerosis and related CNS inflammatory demyelinating diseases.