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局灶性皮质发育不良患者皮质病变中TRPC1的表达模式

Expression Patterns of TRPC1 in Cortical Lesions from Patients with Focal Cortical Dysplasia.

作者信息

Zang Zhenle, Li Song, Zhang Wei, Chen Xin, Zheng Dahai, Shu Haifeng, Guo Wei, Zhao Bangyun, Shen Kaifeng, Wei YuJia, Zheng Xin, Liu Shiyong, Yang Hui

机构信息

Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, 183 Xinqiao Main Street, Shapingba District, Chongqing, 400037, China.

Department of Neurosurgery, Chengdu Military General Hospital of PLA, Chengdu, Sichuan, 610083, China.

出版信息

J Mol Neurosci. 2015 Oct;57(2):265-72. doi: 10.1007/s12031-015-0615-5. Epub 2015 Aug 18.

Abstract

Focal cortical dysplasia (FCD) is known as a common cause of chronic refractory epilepsy, but the underlying mechanisms of the factors that lead to FCD-related epilepsy are unclear. Previous studies have shown that canonical transient receptor potential channels (TRPCs) might be involved in the process of epileptogenesis. Canonical transient receptor potential channel 1 (TRPC1), which is ubiquitously expressed in the brain, has been shown to be involved in epileptiform bust firing in knockout mice. In this study, we examined the expression of TRPC1 in FCD type Ia (FCDIa), FCD type IIa (FCDIIa), and FCD type IIb (FCDIIb) surgical specimens from patients and age-matched autopsy control samples. Real-time quantitative PCR and western blotting indicated that TRPC1 mRNA and protein levels were increased in FCDIa, FCDIIa, and FCDIIb samples compared to control samples. Immunohistochemistry results revealed that TRPC1 was mainly distributed in microcolumns, dysmorphic neurons, and balloon cells. Further double immunofluorescent staining showed that TRPC1 was co-localized with glutamatergic and GABAergic markers. Taken together, our results demonstrate that the overexpression and specific cellular location of TRPC1 might be related to the epileptogenesis of FCD.

摘要

局灶性皮质发育不良(FCD)是慢性难治性癫痫的常见病因,但导致FCD相关癫痫的因素的潜在机制尚不清楚。先前的研究表明,经典瞬时受体电位通道(TRPCs)可能参与癫痫发生过程。经典瞬时受体电位通道1(TRPC1)在大脑中广泛表达,已证实在基因敲除小鼠中参与癫痫样爆发放电。在本研究中,我们检测了TRPC1在来自患者的Ia型FCD(FCDIa)、IIa型FCD(FCDIIa)和IIb型FCD(FCDIIb)手术标本以及年龄匹配的尸检对照样本中的表达。实时定量PCR和蛋白质印迹表明,与对照样本相比,FCDIa、FCDIIa和FCDIIb样本中TRPC1的mRNA和蛋白质水平升高。免疫组织化学结果显示,TRPC1主要分布在微柱、畸形神经元和气球样细胞中。进一步的双重免疫荧光染色表明,TRPC1与谷氨酸能和γ-氨基丁酸能标记物共定位。综上所述,我们的结果表明,TRPC1的过表达和特定细胞定位可能与FCD的癫痫发生有关。

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