Trpc3/6介导Neuregulin-1引起的钙内流参与外周雪旺细胞髓鞘化

The axons of peripheral nervous system are myelinated by Schwann cells.Neuregulin-1 regulates the myelination of Schwann cells by activating calcineurin-NFAT signaling pathways through inducing calcium influx. However, the underlying mechanism of calcium influx induced by neuregulin-1 remains unclear. Our preliminary data have shown that TRPC family were highly expressed in cultured Schwann cells, furthermore, specific inhibitors of TRPC3/6 blocked the calcium influx induced by neuregulin-1 in Schwann cells.Base on these preliminary data, we firstly will further examine the expression of TRPC family in Schwann cells during development using molecular and morphological technologies. Secondly, using calcium imaging, RNAi and western blot, we will examine the roles and mechanism of TRPC3/6 in calcium influx induced by neuregulin-1 in Schwann cells. Finally, we examine the phenotypes of Schwann cell myelination in TRPC konckout mice. These experiments will test our hypothesis: during development, neuregulin-1 induces the calcium influx through TRPC3/6,and activates calcineruin-NFAT signaling pathways, which regulates the myelination of Schwann cells.

外周神经髓鞘化由雪旺细胞完成。Neuregulin-1引起雪旺细胞钙内流，激活Calcineurin-NFAT信号通路，参与雪旺细胞髓鞘化，然而，Neuregulin-1引起钙内流的分子机制不清楚。本课题预实验发现TRPC家族高表达于培养的雪旺细胞中，TRPC3/6抑制剂阻断Neuregulin-1引起的钙内流。拟将在前期工作基础上，采用分子生物学、形态学等实验技术进一步检测TRPC家族在发育过程中雪旺细胞中的表达分布，与髓鞘化的相关性。其次，采用钙离子成像、RNAi干扰、电生理学等方法观察TRPC3/6在Neuregulin-1引起的雪旺细胞钙内流中的作用及其机制。最后，采用体外髓鞘化模型和TRPC3/6基因敲除小鼠，观察TRPC在雪旺细胞髓鞘化中作用的生理学意义。通过上述验证假说：在胚胎发育过程中，TRPC3/6介导Neuregulin-1引起的钙内流，参与雪旺细胞的髓鞘化。

在课题经费资助下，为期一年的研究中，探索了外周雪旺细胞髓鞘化的分子机制，但是由于质粒构建和细胞培养条件所限，进展有些延迟，相关数据和结果正在整理中。同时，结合神经内科的临床与基础，初步探索了神经保护剂丁苯酞在心肌梗死中的保护机制。发现丁苯酞可以有效地抑制心肌梗死时心肌细胞凋亡的发生，从而为临床脑梗死合并心肌梗死的治疗提供了理论支持。文章发表在Acta Physiologica 杂志，影响因子4.32。