P2X7R在局灶性皮质发育不良患者皮质病变中的表达和细胞定位增加

Yujia Wei, W. Guo, Fei-Ji Sun, W. Fu, Dahai Zheng, Xin Chen, Song Li, Zhen-le Zang, Chun-Qing Zhang, Shiyong Liu, Hui Yang
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引用次数: 11

摘要

局灶性皮质发育不良(FCDs)是主要的大脑畸形,通常导致医学上难治性癫痫。嘌呤能嗜电性P2X7受体(P2X7R)是一种非典型的P2X亚型,可抑制钙离子和钠离子。先前的动物研究表明P2X7R是癫痫发生的一个促进因素。本研究旨在确定35例FCD患者手术切除标本中P2X7R相对于尸检对照标本的分布和表达(n = 8)。免疫组织化学共定位分析显示P2X7R主要在神经元、星形胶质细胞和小胶质细胞中表达。在FCD样本中,P2X7R蛋白水平在异常细胞类型中升高,如畸形神经元和球囊细胞,这是FCD的特征。通过实时荧光定量PCR和Western blotting检测,FCD患者标本中P2X7R mRNA和蛋白表达水平较对照组升高;P2X7R在FCDII和FCDIa患者样本中的表达也更高。因为interleukin-1&bgr;是P2X7R信号通路的下游因子,我们确定也存在中强白介素-1;FCD患者病变中畸形神经元、球囊细胞和小胶质细胞的表达。这些结果表明,P2X7R水平的升高可能与人类FCD的发病机制有关,P2X7R可能是一个潜在的抗癫痫靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Increased Expression and Cellular Localization of P2X7R in Cortical Lesions of Patients With Focal Cortical Dysplasia
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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