title: Increased NRG1-ErbB4 signaling in human symptomatic epilepsy.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
authors.forename: Ke-Xin
authors.initials: KX
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China. shuxiacao@zju.edu.cn.
authors.forename: Shu-Xia
authors.initials: SX
authors.lastname: Cao
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
authors.forename: Chen-Jie
authors.initials: CJ
authors.lastname: Shen
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Geng
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
authors.forename: Bi-Qing
authors.initials: BQ
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lian
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China. lixm@zju.edu.cn.|Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China. lixm@zju.edu.cn.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Li
mesh_terms: D000328:Adult; D004827:Epilepsy / Q000378:metabolism* / Q000601:surgery; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000378:metabolism*; D010766:Phosphorylation; D066247:Receptor, ErbB-4 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013702:Temporal Lobe / Q000378:metabolism; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C121001:NR2B NMDA receptor; C094131:NRG1 protein, human; D020890:Neuregulin-1; D016194:Receptors, N-Methyl-D-Aspartate; C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4; D019061:src-Family Kinases