Upregulated Dynamin 1 in an Acute Seizure Model and in Epileptic Patients
Upregulated Dynamin 1 in an Acute Seizure Model and in Epileptic Patients
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急性癫痫模型和癫痫患者中动力 1 上调
DOI：
10.1002/syn.21788
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发表时间：
2015-02-01
期刊：
影响因子：
2.3
通讯作者：
Xiao, Zheng
中科院分区：
文献类型：
--
作者：
Li, Ying-Ying;Chen, Xiao-Ni;Xiao, Zheng
发动蛋白1是一种神经元特异性的鸟苷三磷酸酶（GT3），是突触囊泡再循环和内吞过程中膜分裂的重要组成部分。本研究评估了急性锂-匹罗卡品大鼠模型和颞叶癫痫（TLE）患者中发动蛋白1的表达模式，并研究了改变发动蛋白1表达模式是否会影响体内和体外癫痫发作。免疫荧光、western blot和RT-PCR结果显示，实验组大鼠在癫痫发作后第1 ~ 7天dynamin 1表达水平显著升高，TLE患者dynamin 1表达水平显著升高。行为学研究表明，抑制动力蛋白1可延长首次癫痫发作的潜伏期，降低癫痫发作的频率和严重程度。此外，来自脑切片的电生理记录表明，抑制发动蛋白1降低了无镁诱导的类镁蛋白活性的频率。Dynasore的抗惊厥作用在10 μ M时比在1 μ M或160 μ M时更有效。这些结果表明，发动蛋白1水平的改变可能有助于癫痫发作的发展，并且发动蛋白1活性的靶向调节可能控制癫痫发作。Synapse 69：67-77，2015. (c)2014 Wiley Periodicals，Inc.
Dynamin 1 is a neuron-specific guanosine triphosphatase (GTPase) that is an essential component of membrane fission during synaptic vesicle recycling and endocytosis. This study evaluated the dynamin 1 expression pattern in the acute lithium-pilocarpine rat model and in patients with temporal lobe epilepsy (TLE) and investigated whether altering the dynamin 1 expression pattern affects epileptic seizures in vivo and in vitro. The immunofluorescence, western blot analysis, and reverse transcription-PCR results show that the dynamin 1 expression level increased significantly in experimental rats from day 1 to day 7 after the onset of seizures and was significantly higher in TLE patients. The behavioral study revealed that inhibiting dynamin 1 increased the latency time of the first seizure and decreased the frequency and severity of the seizures. In addition, electrophysiological recordings from brain slices showed that inhibiting dynamin 1 reduces the frequency of Mg-free induced seizure-like activity. The anticonvulsant effect of dynasore was more effective at 10 mu M than at 1 mu M or 160 mu M. These results indicate that the altered level of dynamin 1 may contribute to the development of epileptic seizures and that the targeted regulation of dynamin 1 activity may control epileptic seizures. Synapse 69:67-77, 2015. (c) 2014 Wiley Periodicals, Inc.