Ncx3 Gene Ablation Impairs Oligodendrocyte Precursor Response and Increases Susceptibility to Experimental Autoimmune Encephalomyelitis
Ncx3 Gene Ablation Impairs Oligodendrocyte Precursor Response and Increases Susceptibility to Experimental Autoimmune Encephalomyelitis
复制标题
DOI：
10.1002/glia.22985
复制
发表时间：
2016-07-01
期刊：
影响因子：
6.2
通讯作者：
Boscia, Francesca
中科院分区：
文献类型：
--
作者：
Casamassa, Antonella;La Rocca, Claudia;Boscia, Francesca
Na+/Ca 2+交换器NCX 3是近年来发现的一种髓鞘膜成分，参与了少突胶质细胞成熟过程中[Ca 2 +]i的调节。在此研究了髓鞘少突胶质细胞糖蛋白（MOG）诱导的实验性自身免疫性脑脊髓炎（EAE）（多发性硬化症的动物模型）中的NCX 3参与。在EAE疾病不同阶段的野生型ncx 3（+/+）小鼠中进行的蛋白质印迹和定量共定位研究表明，NCX 3蛋白在慢性阶段强烈上调，其中它与少突胶质细胞前体细胞（OPC）标记物NG 2和髓鞘前化标记物CNX 3强烈共表达。此外，当与ncx 3（+/+）相比时，缺乏ncx 3基因的MOG（35-55）免疫小鼠不仅显示轴突直径减小和完整的髓鞘环数量，而且显示脊髓白色物质中OPC和前髓鞘形成细胞的显著减少。相应地，ncx 3（-/-）和ncx 3（+/-）突变体发展了EAE的早期发作和更严重的临床症状。有趣的是，细胞荧光分析显示，在疾病的高峰期，ncx 3（-/-）小鼠中的免疫T细胞亚群的数量与ncx 3（+/+）中测量的数量没有统计学差异。我们的研究结果表明，敲除NCX 3会损害少突胶质细胞的反应，并减轻EAE的临床症状，而不会改变免疫T细胞群。
The Na+/Ca2+ exchanger NCX3, recently identified as a myelin membrane component, is involved in the regulation of [Ca2+]i during oligodendrocyte maturation. Here NCX3 involvement was studied in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Western blotting and quantitative colocalization studies performed in wild-type ncx3(+/+) mice at different stages of EAE disease showed that NCX3 protein was intensely upregulated during the chronic stage, where it was intensely coexpressed with the oligodendrocyte precursor cells (OPC) marker NG2 and the premyelinating marker CNPase. Moreover, MOG(35-55)-immunized mice lacking the ncx3 gene displayed not only a reduced diameter of axons and an intact myelin ring number but also a dramatic decrease in OPC and pre-myelinating cells in the white matter of the spinal cord when compared with ncx3(+/+). Accordingly, ncx3(-/-) and ncx3(+/-) mutants developed early onset of EAE and more severe clinical symptoms. Interestingly, cytofluorimetric analysis revealed that during the peak stage of the disease, the number of immune T-cell subsets in ncx3(-/-) mice, was not statistically different from that measured in ncx3(+/+). Our findings demonstrate that knocking-out NCX3 impairs oligodendrocyte response and worsens clinical symptoms in EAE without altering the immune T-cell population.