Wang Dan, Ren Min, Guo Jiamei, Yang Guang, Long Xianghua, Hu Rong, Shen Wenjing, Wang Xuefeng, Zeng Kebin
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.
Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PLoS One. 2014 Dec 23;9(12):e115801. doi: 10.1371/journal.pone.0115801. eCollection 2014.
To explore the effects of neuronal Per-Arnt-Sim domain protein 4 (Npas4) on seizures in pilocarpine-induced epileptic rats, Npas4 expression was detected by double-label immunofluorescence, immunohistochemistry, and Western blotting in the brains of pilocarpine-induced epileptic model rats at 6 h, 24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after status epilepticus. Npas4 was localized primarily in the nucleus and in the cytoplasm of neurons. The Npas4 protein levels increased in the acute phase of seizures (between 6 h and 72 h) and decreased in the chronic phases (between 7 d and 60 d) in the rat model. Npas4 expression was knocked down by specific siRNA interference. Then, the animals were treated with pilocarpine, and the effects on seizures were evaluated on the 7th day. The onset latencies of pilocarpine-induced seizures were decreased, while the seizure frequency, duration and attack rate increased in these rats. Our study indicates that Npas4 inhibits seizure attacks in pilocarpine-induced epileptic rats.
为探究神经元芳香烃受体核转运蛋白4（Npas4）对匹鲁卡品诱导的癫痫大鼠癫痫发作的影响，采用双标免疫荧光、免疫组织化学和蛋白质免疫印迹法检测癫痫持续状态后6小时、24小时、72小时、7天、14天、30天和60天的匹鲁卡品诱导的癫痫模型大鼠脑内Npas4的表达。Npas4主要定位于神经元的细胞核和细胞质中。在大鼠模型中，癫痫发作急性期（6小时至72小时之间）Npas4蛋白水平升高，慢性期（7天至60天之间）降低。通过特异性小干扰RNA（siRNA）干扰敲低Npas4表达。然后，用匹鲁卡品处理动物，并在第7天评估对癫痫发作的影响。这些大鼠匹鲁卡品诱导的癫痫发作的起始潜伏期缩短，而癫痫发作频率、持续时间和发作率增加。我们的研究表明，Npas4抑制匹鲁卡品诱导的癫痫大鼠的癫痫发作。
