Expression of pannexin 1 and 2 in cortical lesions from intractable epilepsy patients with focal cortical dysplasia.
Expression of pannexin 1 and 2 in cortical lesions from intractable epilepsy patients with focal cortical dysplasia.
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顽固性癫痫局灶性皮质发育不良患者皮质病变中pannexin 1和2的表达
DOI：
10.18632/oncotarget.14317
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发表时间：
2017-01-24
期刊：
影响因子：
--
通讯作者：
Liu S
中科院分区：
文献类型：
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作者：
Li S;Zang Z;He J;Chen X;Yu S;Pei Y;Hou Z;An N;Yang H;Zhang C;Liu S
局灶性皮质发育不良（FCD）是儿童难治性癫痫的主要原因，但其发病机制及诱发癫痫的机制尚不清楚。越来越多的证据表明，大孔离子通道，泛连接蛋白1（Panx 1）和2（Panx 2），参与癫痫和大脑发育。在本研究中，我们研究了来自FCD Ia型（FCDIa）、IIa型（FCDIIa）和IIb型（FCDIIb）患者的手术样本以及年龄匹配的尸检对照样本中Panx 1和Panx 2的表达。我们发现Panx1 mRNA和蛋白水平在所有这些FCD样品中均增加。免疫组化结果显示，Panx 1主要分布于微柱神经元、畸形神经元（DNs）、气球样细胞（BC）和反应性星形胶质细胞中。双标染色显示Panx 1阳性神经元主要为多巴胺能神经元，偶见正常形态的GABA能神经元。重要的是，Panx 1蛋白水平与癫痫发作频率呈正相关。有趣的是，Panx 2 mRNA和蛋白水平仅在FCDIIb病变中上调，并在SOX 2阳性多能BC上特征性表达。免疫荧光实验表明，Panx 2阳性的BCs主要表达神经元分化转录因子MASH 1，但不表达未成熟的胶质细胞标志物波形蛋白。总之，我们的研究结果建立了一个潜在的作用，具体的表达和细胞分布模式的Panx1和Panx2 FCD相关的癫痫发生和发病机制。
Focal cortical dysplasia (FCD) is a major cause of intractable epilepsy in children however the mechanisms underlying the pathogenesis of FCD and FCD induced epilepsy remain unclear. Increasing evidence suggests that the large-pore ion channels, pannexin 1 (Panx1) and 2 (Panx2), are involved in epilepsy and brain development. In this study, we investigated the expression of Panx1 and Panx2 in surgical samples from patients with FCD type Ia (FCDIa), type IIa (FCDIIa), and type IIb (FCDIIb) and in age-matched autopsy control samples. We found Panx1 mRNA and protein levels were both increased in all these FCD samples. Immunohistochemical analyses revealed that Panx1 was mainly distributed in microcolumn neurons, dysmorphic neurons (DNs), balloon cells (BCs) and reactive astrocytes. Double-labeled staining showed that the Panx1-positive neurons were mostly glutamatergic DNs and occasionally GABAergic normal-appearing neurons. Importantly, the protein levels of Panx1 positively correlated with the frequency of seizures. Intriguingly, the Panx2 mRNA and protein levels were only upregulated in FCDIIb lesions and characteristically expressed on SOX2-positive multipotential BCs. Immunofluorescent experiments identified that Panx2-positive BCs mainly expressed the neuronal differentiation transcription factor MASH1 but not the immature glial marker vimentin. Taken together, our results established a potential role of the specific expression and cellular distribution patterns of Panx1 and Panx2 in FCD-associated epileptogenesis and pathogenesis.