12月11日,，國際著名雜志《自然·神經(jīng)科學》Nature Neuroscience在線發(fā)表了中科院上海生科院神經(jīng)所研究人員的最新研究成果“Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons,。”,，領(lǐng)導這一研究的是熊志奇研究組的譚國鶴和劉媛媛等,，他們研究發(fā)現(xiàn)關(guān)于神經(jīng)調(diào)節(jié)素1（Neuregulin-1,，NRG1）在癲癇發(fā)生過程中行使負反饋的調(diào)控機制,。
神經(jīng)電活動依賴的多肽類生長因子在體內(nèi)的表達在癲癇發(fā)生發(fā)展的過程中起著重要作用,例如,，腦源性神經(jīng)營養(yǎng)因子（BDNF）可以促進癲癇的產(chǎn)生,。然而,，哪些生長因子在這個過程中起著有力的反向制衡作用卻是未知的。
熊志奇研究組與美國Georgia Health Sciences University分子醫(yī)學研究所的梅林教授實驗室合作,，發(fā)現(xiàn)在不同的癲癇模型,、不同種屬的嚙齒類動物中癲癇發(fā)作都可以上調(diào)腦內(nèi)Nrg1基因的表達及其受體ErbB4的酪氨酸磷酸化。通過結(jié)合藥理學和基因操作的手段作者們發(fā)現(xiàn),，NRG1是顳葉癲癇病理進程中的一個關(guān)鍵的內(nèi)源性抑制性因子,，它通過激活小清蛋白陽性中間神經(jīng)元上的ErbB4受體，對癲癇發(fā)生起到重要的負反饋調(diào)節(jié)作用,。為預防和治療癲癇提供了可能的新靶標,。該研究得到了中國科學院、科技部和國家自然科學基金委等機構(gòu)支持,。（生物谷Bioon.com）
doi:10.1038/nn.3005
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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.
