Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
Synapse. 2012 Jul;66(7):622-9. doi: 10.1002/syn.21548. Epub 2012 Mar 30.
The gene encoding dystrobrevin-binding-protein-1 (dysbindin) is expressed in many areas of the central nervous system and plays a role in intracellular vesicle trafficking, synaptic vesicle trafficking, and neurotransmitter release. At a cellular level, dysbindin is thought to mediate presynaptic glutamatergic transmission. Using Western blotting and immunofluorescence, we investigated dysbindin expression in brain tissues of the patients with temporal lobe epilepsy (TLE) and rats with TLE (lithium chloride pilocarpine model) to explore its possible role in epileptogenesis. Twenty-five samples of temporal neocortex from patients undergoing surgery for drug-refractory TLE epilepsy and 10 histologically normal temporal lobes tissues from control subjects were used in our study. We also examined dysbindin expression in the hippocampus and adjacent cortex from experimental Sprague-Dawley rats. Dysbindin was expressed in the cytoplasm of neurons from epileptic specimens, and levels of dysbindin proteins were significantly increased in patients with TLE. Dysbindin was also expressed in the neurons of the hippocampus and adjacent cortex from experimental and control rats. Western blotting of rat brain tissue showed that dysbindin was upregulated gradually from 6 h after kindling. Maximal expression was seen around 2 months in chronic epileptic phase. These results demonstrated that the increased expression of dysbindin might play a role in the pathogenesis of drug-refractory TLE.
编码肌联蛋白结合蛋白-1（dysbindin）的基因在中枢神经系统的许多区域表达，在细胞内囊泡运输、突触囊泡运输和神经递质释放中发挥作用。在细胞水平上，dysbindin 被认为介导突触前谷氨酸能传递。我们使用 Western blot 和免疫荧光技术研究了颞叶癫痫（TLE）患者和 TLE 大鼠（氯化锂匹罗卡品模型）脑组织中的 dysbindin 表达，以探讨其在癫痫发生中的可能作用。我们的研究使用了 25 例接受手术治疗药物难治性 TLE 癫痫患者的颞叶新皮质样本和 10 例来自对照受试者的组织学正常颞叶组织。我们还检查了来自实验性 Sprague-Dawley 大鼠海马体和邻近皮质的 dysbindin 表达。dysbindin 在癫痫标本神经元的细胞质中表达，TLE 患者的 dysbindin 蛋白水平显著增加。dysbindin 也在实验和对照大鼠的海马体和邻近皮质的神经元中表达。大鼠脑组织的 Western blot 显示，自点燃后 6 小时起 dysbindin 逐渐上调。在慢性癫痫期约 2 个月时达到最大表达。这些结果表明，dysbindin 的表达增加可能在药物难治性 TLE 的发病机制中发挥作用。
