N-Cadherin is Involved in Neuronal Activity-Dependent Regulation of Myelinating Capacity of Zebrafish Individual Oligodendrocytes In Vivo
N-Cadherin is Involved in Neuronal Activity-Dependent Regulation of Myelinating Capacity of Zebrafish Individual Oligodendrocytes In Vivo
复制标题
N-钙粘蛋白参与体内斑马鱼个体少突胶质细胞髓鞘形成能力的神经元活动依赖性调节
DOI：
10.1007/s12035-016-0233-4
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发表时间：
2017-11-01
影响因子：
5.1
通讯作者：
Hu, Bing
中科院分区：
文献类型：
--
作者：
Chen, Min;Xu, Yang;Hu, Bing
刺激神经元活动增加单个少突胶质细胞的髓鞘形成，但在体内髓鞘形成如何由神经元活动调节仍不完全清楚。虽然体外研究已经揭示了N-钙粘素在髓鞘形成中的重要作用，但我们在体内的了解仍然相当有限。为了获得N-钙粘素在个体少突胶质细胞髓鞘形成能力的活性依赖性调节中的作用，我们成功地在斑马鱼中枢神经系统亚细胞结构水平建立了Mauthner细胞的体内动态成像模型。用增强型绿色荧光蛋白(EGFP)标记的N-钙粘蛋白在单细胞水平上显示N-钙粘蛋白在单细胞水平的稳定蓄积和移动转运。我们发现，戊四氮(PTZ)显著增加了N-钙粘素在Mauthner轴突中的积聚，这一反应与增加每个少突胶质细胞的鞘数目平行。通过使用阻断N-钙粘蛋白功能的寡肽(AHAVD)抵消这种表型，我们表明PTZ以一种N-钙粘素依赖的方式调节髓鞘形成。此外，我们进一步认为PTZ通过cAMP途径影响N-钙粘素和髓鞘形成。因此，我们的数据表明，N-钙粘附素参与了体内斑马鱼个体少突胶质细胞髓鞘形成能力的神经元活性依赖性调节。
Stimulating neuronal activity increases myelin sheath formation by individual oligodendrocytes, but how myelination is regulated by neuronal activity in vivo is still not fully understood. While in vitro studies have revealed the important role of N-cadherin in myelination, our understanding in vivo remains quite limited. To obtain the role of N-cadherin during activity-dependent regulation of myelinating capacity of individual oligodendrocytes, we successfully built an in vivo dynamic imaging model of the Mauthner cell at the subcellular structure level in the zebrafish central nervous system. Enhanced green fluorescent protein (EGFP)-tagged N-cadherin was used to visualize the stable accumulations and mobile transports of N-cadherin by single-cell electroporation at the single-cell level. We found that pentylenetetrazol (PTZ) significantly enhanced the accumulation of N-cadherin in Mauthner axons, a response that was paralleled by enhanced sheath number per oligodendrocytes. By offsetting this phenotype using oligopeptide (AHAVD) which blocks the function of N-cadherin, we showed that PTZ regulates myelination in an N-cadherin-dependent manner. What is more, we further suggested that PTZ influences N-cadherin and myelination via a cAMP pathway. Consequently, our data indicated that N-cadherin is involved in neuronal activity-dependent regulation of myelinating capacity of zebrafish individual oligodendrocytes in vivo.