The Inhibitory Effects of Npas4 on Seizures in Pilocarpine-Induced Epileptic Rats |
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Authors: | Dan Wang Min Ren Jiamei Guo Guang Yang Xianghua Long Rong Hu Wenjing Shen Xuefeng Wang Kebin Zeng |
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Institution: | 1. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.; 2. Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.; Université Pierre et Marie Curie, France, |
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Abstract: | 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. |
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