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颞叶癫痫患者和匹罗卡品诱导的大鼠模型中 Gab2 表达降低。

Decreased expression of Gab2 in patients with temporal lobe epilepsy and pilocarpine-induced rat model.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

出版信息

Synapse. 2014 Apr;68(4):168-77. doi: 10.1002/syn.21725. Epub 2013 Dec 20.

Abstract

Growth factor receptor bound protein-2 associated binding protein-2 (Gab2) is widely expressed in the central nervous system, and participates in multiple signaling pathways. Recent studies showed that Gab2 was involved in the pathogenesis of Alzheimer's disease (AD). Gab2 reduces tau phosphorylation levels and is associated with cellular apoptosis and differentiation. However, whether Gab2 was also involved in the pathogenesis of epilepsy, remains unknown. This study aimed to investigate the expression pattern of Gab2 protein in brains with temporal lobe epilepsy (TLE) and in pilocarpine-induced rat model of TLE. Western blot, immunohistochemistry, and immunofluorescence were used to assess the location and the expression level of Gab2 in the neocortex of the temporal lobe in patients with TLE and in rat model of epilepsy. Results showed that Gab2 protein was expressed mainly in the membranes and cytoplasm of neurons in the cortex and hippocampus. Gab2 protein expression was remarkably reduced in temporal neocortex of TLE patients. In hippocampus and adjacent cortex in rat epilepsy model, Gab2 expression was decreased at different time points after kindling compared with the controls, and the lowest level of Gab2 expression occurred at 1 week. Thus, significant reductions of Gab2 protein in both TLE patients and epilepsy rats suggest that Gab2 may play an important role in the pathogenesis of TLE.

摘要

生长因子受体结合蛋白-2 相关结合蛋白-2(Gab2)广泛表达于中枢神经系统,参与多种信号通路。最近的研究表明,Gab2 参与了阿尔茨海默病(AD)的发病机制。Gab2 可降低 tau 磷酸化水平,并与细胞凋亡和分化有关。然而,Gab2 是否也参与了癫痫的发病机制尚不清楚。本研究旨在探讨 Gab2 蛋白在颞叶癫痫(TLE)患者大脑中的表达模式,以及在匹罗卡品诱导的 TLE 大鼠模型中的表达模式。采用 Western blot、免疫组化和免疫荧光技术检测 TLE 患者颞叶皮质和癫痫大鼠模型中 Gab2 蛋白的定位和表达水平。结果表明,Gab2 蛋白主要表达于皮质和海马神经元的膜和细胞质中。TLE 患者颞叶皮质中 Gab2 蛋白表达显著减少。在癫痫大鼠模型的海马和邻近皮质中,与对照组相比,点燃后不同时间点 Gab2 表达降低,Gab2 表达最低水平出现在 1 周。因此,TLE 患者和癫痫大鼠中 Gab2 蛋白的显著减少表明,Gab2 可能在 TLE 的发病机制中发挥重要作用。

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