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神经纤维瘤蛋白在大鼠毛果芸香碱诱导的癫痫模型中调节癫痫发作

Neurofibromin Regulates Seizure Attacks in the Rat Pilocarpine-Induced Model of Epilepsy.

作者信息

Ren Min, Li Kunyi, Wang Dan, Guo Jiamei, Li Jing, Yang Guang, Long Xianghua, Shen Wenjing, Hu Rong, Wang Xuefeng, Zeng Kebin

机构信息

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Youyi Road 1#, Yuzhong County, Chongqing, 400016, China.

Department of Neurology, Xinhua Hospital of Hubei Province, Hubei, 430000, China.

出版信息

Mol Neurobiol. 2016 Nov;53(9):6069-6077. doi: 10.1007/s12035-015-9503-9. Epub 2015 Nov 4.

Abstract

Studies have shown that neurofibromin (NF1) restricts GABA release at inhibitory synapses and regulates dendritic spine formation, which may play an important role in temporal lobe epilepsy (TLE). NF1 expression was detected by double-label immunofluorescence, immunohistochemistry, and western blot analysis in the brains of pilocarpine-induced epilepsy model rats at 6 h, 24 h, 72 h, 7 days, 14 days, 30 days, and 60 days after kindling. NF1 was localized primarily in the nucleus and cytoplasm of neurons. NF1 protein levels significantly increased in the chronic phase (from 7 days until 60 days) in this epileptic rat model. After NF1 expression was knocked down by specific siRNA, the effects of kindling with pilocarpine were evaluated on the 7th day after kindling. The onset latencies of pilocarpine-induced seizures were elevated, and the seizure frequency and duration were reduced in these rats. Our study demonstrates that NF1 promoted seizure attacks in rats with pilocarpine-induced epilepsy.

摘要

研究表明,神经纤维瘤蛋白(NF1)可限制抑制性突触处的GABA释放并调节树突棘形成,这可能在颞叶癫痫(TLE)中起重要作用。通过双标免疫荧光、免疫组织化学和蛋白质印迹分析,在匹罗卡品诱导的癫痫模型大鼠脑内点燃后6小时、24小时、72小时、7天、14天、30天和60天检测NF1表达。NF1主要定位于神经元的细胞核和细胞质中。在该癫痫大鼠模型的慢性期(从7天至60天),NF1蛋白水平显著升高。在用特异性siRNA敲低NF1表达后,在点燃后第7天评估匹罗卡品点燃的效果。这些大鼠中,匹罗卡品诱导癫痫发作的起始潜伏期延长,癫痫发作频率和持续时间缩短。我们的研究表明,NF1促进了匹罗卡品诱导癫痫大鼠的癫痫发作。

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