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.

中文翻译：

---

MS 灰质病变的 MicroRNA 谱可识别突触蛋白 Synaptotagmin-7 的调节剂。

我们在灰质和白质多发性硬化症 (MS) 病变中建立了 microRNA (miRNA) 谱，并鉴定了 7 种在灰质病变中显着上调的 miRNA。这七个 miRNA 中的五个，miR-330-3p、miR-4286、miR-4488、let-7e-5p、miR-432-5p 共享共同的目标突触结合蛋白 7 (Syt7)。使用纳米线技术的免疫组织化学和转录物分析揭示了 Syt7 的分布不均，Syt7 在神经元胞体中积累，在轴突结构中表达降低。这种分布不均至少可以部分由轴突 Syt7 运输障碍来解释。由于 Syt7 是一种突触相关分子，这种分布不均可能导致 MS 患者的神经元功能受损。因此，我们的结果导致假设这五种 miRNA 在灰质病变中的过度表达是进一步减少内源性神经元 Syt7 产生的细胞机制。因此，miRNA 似乎在 MS 中作为神经元结构的调节剂发挥着重要作用。