12月11日，国际著名杂志《自然·神经科学》Nature Neuroscience在线发表了中科院上海生科院神经所研究人员的最新研究成果“Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons。”，领导这一研究的是熊志奇研究组的谭国鹤和刘媛媛等，他们研究发现关于神经调节素1（Neuregulin-1，NRG1）在癫痫发生过程中行使负反馈的调控机制。
神经电活动依赖的多肽类生长因子在体内的表达在癫痫发生发展的过程中起着重要作用,例如，脑源性神经营养因子（BDNF）可以促进癫痫的产生。然而，哪些生长因子在这个过程中起着有力的反向制衡作用却是未知的。
熊志奇研究组与美国Georgia Health Sciences University分子医学研究所的梅林教授实验室合作，发现在不同的癫痫模型、不同种属的啮齿类动物中癫痫发作都可以上调脑内Nrg1基因的表达及其受体ErbB4的酪氨酸磷酸化。通过结合药理学和基因操作的手段作者们发现，NRG1是颞叶癫痫病理进程中的一个关键的内源性抑制性因子，它通过激活小清蛋白阳性中间神经元上的ErbB4受体，对癫痫发生起到重要的负反馈调节作用。为预防和治疗癫痫提供了可能的新靶标。该研究得到了中国科学院、科技部和国家自然科学基金委等机构支持。（生物谷Bioon.com）
doi:10.1038/nn.3005
PMC:
PMID:
Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons
Guo-He Tan,Yuan-Yuan Liu,Xiao-Ling Hu,Dong-Min Yin,Lin Mei& Zhi-Qi Xiong
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 CaMKIIα-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.
