Institute of Neuropathology, University Hospital Essen, D-45147, Essen, Germany.
Institute of Pathology, University Hospital Essen, D-45147, Essen, Germany.
Brain Pathol. 2020 May;30(3):524-540. doi: 10.1111/bpa.12800. Epub 2019 Nov 17.
We established microRNA (miRNA) profiles in gray and white matter multiple sclerosis (MS) lesions and identified seven miRNAs which were significantly more upregulated in the gray matter lesions. Five of those seven miRNAs, miR-330-3p, miR-4286, miR-4488, let-7e-5p, miR-432-5p shared the common target synaptotagmin7 (Syt7). Immunohistochemistry and transcript analyses using nanostring technology revealed a maldistribution of Syt7, with Syt7 accumulation in neuronal soma and decreased expression in axonal structures. This maldistribution could be at least partially explained by an axonal Syt7 transport disturbance. Since Syt7 is a synapse-associated molecule, this maldistribution could result in impairment of neuronal functions in MS patients. Thus, our results lead to the hypothesis that the overexpression of these five miRNAs in gray matter lesions is a cellular mechanism to reduce further endogenous neuronal Syt7 production. Therefore, miRNAs seem to play an important role as modulators of neuronal structures in MS.
我们建立了多发性硬化症（MS）灰质和白质病变中的 microRNA（miRNA）图谱，并鉴定出七个在灰质病变中明显上调的 miRNA。这七个 miRNA 中有五个，miR-330-3p、miR-4286、miR-4488、let-7e-5p、miR-432-5p，它们有一个共同的靶基因突触结合蛋白 7（Syt7）。使用纳米串技术进行免疫组织化学和转录分析表明，Syt7 分布异常，神经元胞体中 Syt7 积累，轴突结构中 Syt7 表达减少。这种分布异常至少可以部分解释为 Syt7 的轴突运输障碍。由于 Syt7 是一种突触相关分子，这种分布异常可能导致 MS 患者神经元功能受损。因此，我们的研究结果提出了一个假设，即在灰质病变中这五个 miRNA 的过表达是一种细胞机制，可减少内源性神经元 Syt7 的产生。因此，miRNA 似乎在 MS 中神经元结构的调节中发挥重要作用。
