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

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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.

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Acknowledgments

The study was supported by Chongqing Health Bureau Fund, China (No. 2011-2-118 to KBZ), a grant from Science Foundation of Chongqing Science and Technology Commission, China (No. CSTC2012jjA10065 to KBZ), and the National Key Clinical Specialty Discipline Construction Program of China to the Department of Neurology, the First Affiliated Hospital of Chongqing Medical University. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

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

      Min Ren, Kunyi Li, Xianghua Long, Wenjing Shen, Rong Hu, Xuefeng Wang & Kebin Zeng

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

      Dan Wang

    3. Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

      Jiamei Guo & Jing Li

    4. Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

      Guang Yang

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    1. Min Ren
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    Correspondence to Kebin Zeng.

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    The experimental procedures of this study were approved by the Commission of Chongqing Medical University for ethics in animal experiments.

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    Min Ren and Kunyi Li contributed equally to this work.

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    Ren, M., Li, K., Wang, D. et al. Neurofibromin Regulates Seizure Attacks in the Rat Pilocarpine-Induced Model of Epilepsy. Mol Neurobiol 53, 6069–6077 (2016). https://doi.org/10.1007/s12035-015-9503-9

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