Increased NRG1-ErbB4 signaling in human symptomatic epilepsy.
Increased NRG1-ErbB4 signaling in human symptomatic epilepsy.
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人类症状性癫痫中 NRG1-ErbB4 信号传导增强
DOI：
10.1038/s41598-017-00207-7
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发表时间：
2017-03-10
影响因子：
4.6
通讯作者：
Li XM
中科院分区：
文献类型：
--
作者：
Zhu JM;Li KX;Cao SX;Chen XJ;Shen CJ;Zhang Y;Geng HY;Chen BQ;Lian H;Zhang JM;Li XM
以往的研究表明，神经调节蛋白1(NRG1)-ErbB4信号通路可能调节额叶皮质快峰神经元的兴奋性，参与原发癫痫的发病机制。然而，NRG1/ErbB4在人类症状性癫痫中的确切作用和机制仍不清楚。利用新鲜的人类症状性癫痫组织，我们发现NRG1和ErbB4在颞叶皮质的蛋白水平显著增加。此外，在人类症状性癫痫组织中，NRG1-ErbB4信号抑制了1472位GluN2B的磷酸化，并通过Src激酶抑制了GluN2B和Src的磷酸化水平。我们的研究揭示了NRG1-ErbB4信号通路在症状性癫痫中的关键作用，这与原发性癫痫不同，我们认为NRG1-ErbB4信号可能是一种动态平衡调节剂，保护大脑免受癫痫样活动加剧的影响。
Previous studies have shown that the neuregulin 1 (NRG1)-ErbB4 signaling pathway may regulate the excitability of fast-spiking neurons in the frontal cortex and participate in primary epilepsy pathogenesis. However, the exact roles and mechanism for NRG1/ErbB4 in human symptomatic epilepsy are still unclear. Using fresh human symptomatic epilepsy tissues, we found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex. In addition, NRG1-ErbB4 signaling suppressed phosphorylation of GluN2B at position 1472 by Src kinase, and decreased levels of phosphorylation level of GluN2B and Src were detected in human symptomatic epilepsy tissues. Our study revealed a critical role of the NRG1-ErbB4 signaling pathway in symptomatic epilepsy, which is different from that in primary epilepsy, and we propose that the NRG1-ErbB4 signaling may act as a homeostasis modulator that protects the brain from aggravation of epileptiform activity.