Increased Expression and Cellular Localization of P2X7R in Cortical Lesions of Patients With Focal Cortical Dysplasia
Increased Expression and Cellular Localization of P2X7R in Cortical Lesions of Patients With Focal Cortical Dysplasia
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局灶性皮质发育不良患者皮质病变中 P2X7R 的表达增加和细胞定位
DOI：
10.1093/jnen/nlv003
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发表时间：
2016-01
影响因子：
3.2
通讯作者：
Yang, Hui
中科院分区：
文献类型：
--
作者：
Zang, Zhen-Le;Zhang, Chun-Qing;Liu, Shi-Yong;Yang, Hui
局灶性皮质发育不良（FCD）是一种主要的脑畸形，通常会导致药物难治性癫痫。嘌呤能亲离子型P2 X7受体（P2 X7 R）是一种非典型的P2 X亚型，门控钙和钠离子。以前的动物研究表明，P2 X7 R是癫痫发生的一个促成因素。本研究旨在确定35例FCD患者手术切除标本相对于尸检对照样本（n = 8）中P2 X7 R的分布和表达。免疫组织化学共定位分析显示，P2 X7 R主要表达在神经元，星形胶质细胞和小胶质细胞。在FCD样本中，P2 X7 R蛋白水平在异常细胞类型中增加，例如畸形神经元和气球细胞，这是FCD的特征。通过实时PCR和蛋白质印迹，P2 X7 R mRNA和蛋白质表达水平在FCD患者样品中相对于对照样品升高; P2 X7 R表达在FCDII患者样品中也高于FCDIa患者样品。由于白细胞介素-1是P2 X7 R信号通路的下游因子，我们确定在FCD患者病变的畸形神经元、球囊细胞和小胶质细胞中也有中等至强的白细胞介素-1表达。这些结果表明，增加P2 X7 R水平可能有助于人类FCD的发病机制，P2 X7 R代表了潜在的抗癫痫靶点。
Focal cortical dysplasias (FCDs) are major brain malformations that commonly lead to medically intractable epilepsy. The purinergic ionotropic P2X7 receptor (P2X7R) is an atypical P2X subtype that gates calcium and sodium ions. Previous animal studies have suggested that P2X7R is a contributing factor in epileptogenesis. This study aimed to define the distribution and expression of P2X7R in 35 FCD patient-surgical-resection specimens relative to autopsy control samples (n = 8). Immunohistochemical colocalization assays revealed that P2X7R was primarily expressed in neurons, astrocytes, and microglia. In FCD samples, P2X7R protein levels were increased in abnormal cell types such as dysmorphic neurons and balloon cells, which are characteristic of FCD. By real-time PCR and Western blotting, P2X7R mRNA and protein expression levels were elevated in FCD patient samples vs control samples; P2X7R expression was also higher in FCDII vs FCDIa patient samples. Because interleukin-1&bgr; is a downstream factor of the P2X7R signaling pathway, we determined that there was also moderate-to-strong interleukin-1&bgr; expression in the dysmorphic neurons, balloon cells, and microglia in FCD patient lesions. These results indicate that increasing P2X7R levels may contribute to the pathogenesis of human FCD and that P2X7R represents a potential anti-epileptogenic target.
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影响因子：
5.6
作者：
Vezzani, A;Moneta, D;De Simoni, MG
通讯作者：
De Simoni, MG
影响因子：
5.6
作者：
E. Vianna;A. T. Ferreira-A. T.-Ferreira-2110794576;M. Naffah-Mazzacoratti;E. Sanabria;M. Funke;E. Cavalheiro;M. Fernandes
通讯作者：
E. Vianna;A. T. Ferreira-A. T.-Ferreira-2110794576;M. Naffah-Mazzacoratti;E. Sanabria;M. Funke;E. Cavalheiro;M. Fernandes
影响因子：
2.9
作者：
P. Rappold;E. Lynd-Balta;E. Lynd-Balta;S. Joseph
通讯作者：
P. Rappold;E. Lynd-Balta;E. Lynd-Balta;S. Joseph
影响因子：
5.3
作者：
Avignone, Elena;Ulmann, Lauriane;Audinat, Etienne
通讯作者：
Audinat, Etienne
影响因子：
1.7
作者：
Cho, Jin-Hwa;Choi, In-Sun;Jang, Il-Sung
通讯作者：
Jang, Il-Sung