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Title: Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons
Author: Tan, Guo-He ; Liu, Yuan-Yuan ; Hu, Xiao-Ling ; Yin, Dong-Min ; Mei, Lin ; null(熊志奇)
Source: NATURE NEUROSCIENCE
Issued Date: 2012
Volume: 15, Issue:2, Pages:258-266
Keyword: SCHIZOPHRENIA-LIKE PSYCHOSIS ; NMDA RECEPTORS ; KNOCKOUT MICE ; EPILEPSY ; RAT ; BRAIN ; MODEL ; HIPPOCAMPUS ; PLASTICITY ; SEIZURES
Subject: Neurosciences & Neurology
Corresponding Author: Mei, L (reprint author), Georgias Hlth Sci Univ, Program Dev Neurobiol, Inst Mol Med & Genet, Augusta, GA 30912 USA,lmei@georgiahealth.edu ; xiongzhiqi@ion.ac.cn
English Abstract: Epilepsy is a common and refractory neurological disorder, but the neuronal regulatory mechanisms of epileptogenesis remain largely unclear. Activity-dependent transcription of genes for neurotrophins such as brain-derived neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however, little is known about factors that may act as intrinsic, homeostatic or counterbalancing mechanisms. Using rodent models, here we show that limbic seizure activity upregulated NRG1-ErbB4 signaling and that epileptogenesis was inhibited by infusing NRG1 intracerebrally but exacerbated by neutralizing endogenous NRG1 with soluble ErbB4 extracellular domain, by inhibiting ErbB4 activation or by deleting the Erbb4 gene. Furthermore, specific depletion of ErbB4 in parvalbumin-expressing interneurons abolished NRG1-mediated inhibition of epileptogenesis and promoted kindling progression, resulting in increased spontaneous seizures and exuberant mossy fiber sprouting. In contrast, depleting ErbB4 in CaMKII alpha-positive pyramidal neurons had no effect. Thus, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1506
Appears in Collections:神经所(总)_期刊论文
疾病神经生物学研究组_期刊论文

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Recommended Citation:
Tan, Guo-He; Liu, Yuan-Yuan; Hu, Xiao-Ling; Yin, Dong-Min; Mei, Lin; Xiong, Zhi-Qi.Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons,NATURE NEUROSCIENCE,2012,15(2):258-266
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