研究发现神经胶质瘤中电信号与突触信号的整合

　　发布时间：2019年9月19日 来源：科学网

　　美国斯坦福大学Michelle Monje小组的一项最新研究发现神经胶质瘤中的电信号与突触信号能够整合进神经回路中。该研究于2019年9月18日在线发表于《自然》。

　　研究人员发现神经元和神经胶质瘤相互作用包括通过真正的AMPA受体依赖性神经元与神经胶质瘤突触之间的电化学通信。神经元活动还引起非突触活性依赖性钾电流，其通过间隙连接介导的肿瘤互连扩增，形成电耦合网络。通过体内光遗传学检测到的神经胶质瘤膜的去极化促进增殖，而药理或遗传阻断的电化学信号传导能够抑制神经胶质瘤异种移植物的生长并延长小鼠存活。

　　这项工作强调了胶质瘤增加神经元兴奋性和活动调节胶质瘤生长的积极反馈机制，此外人类术中皮层脑电图也显示胶质瘤浸润脑中皮质兴奋性增加。总之，这些发现表明神经回路中突触和电信号的整合能够促进胶质瘤进展。

　　据了解，高级别胶质瘤是致命的脑癌，其进展受到神经元活动的强烈调节。活动调节的生长因子释放促进胶质瘤生长，但仅此不足以解释神经元活动对胶质瘤进展的影响。

　　附：英文原文

　　Title: Electrical and synaptic integration of glioma into neural circuits

　　Author: Humsa S. Venkatesh, Wade Morishita, Anna C. Geraghty, Dana Silverbush, Shawn M. Gillespie, Marlene Arzt, Lydia T. Tam, Cedric Espenel, Anitha Ponnuswami, Lijun Ni, Pamelyn J. Woo, Kathryn R. Taylor, Amit Agarwal, Aviv Regev, David Brang, Hannes Vogel, Shawn Hervey-Jumper, Dwight E. Bergles, Mario L. Suv, Robert C. Malenka, Michelle Monje

　　Issue&Volume: 2019-09-18

　　Abstract:

　　High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron–glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.