Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced Inhibition In vitro.
Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced Inhibition In vitro.
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DOI：
10.1038/s41598-018-29069-3
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发表时间：
2018-07-19
影响因子：
4.6
通讯作者：
Karumbaiah L
中科院分区：
文献类型：
--
作者：
Latchoumane CV;Jackson L;Sendi MSE;Tehrani KF;Mortensen LJ;Stice SL;Ghovanloo M;Karumbaiah L
功能性电刺激（FES）作为介导受损中枢神经系统（CNS）修复和恢复的治疗工具正迅速获得关注。然而，这些刺激模式在分子、细胞和网络水平上的潜在机制和影响在很大程度上仍然未知。在这项研究中，我们使用胚胎干细胞（ESC）衍生的神经元和神经胶质细胞的共培养，以研究网络的成熟后，急性管理的L-谷氨酸，这是一个已知的介质兴奋性毒性中枢神经系统损伤。然后，我们使用慢性低频刺激（LFS）和直流电刺激（DCS）协议调制网络成熟。我们证明，L-谷氨酸损害的ESC衍生的神经元和神经胶质细胞的成熟率立即和超过一个星期后，急性治疗。单独给予LFS和DCS方案后，L-谷氨酸输注显着促进神经元的兴奋性以及网络同步性，而LFS/DCS的组合没有。qRT-PCR分析显示，LFS和DCS单独作用可显著上调兴奋性和可塑性相关转录本N-甲基-D-天冬氨酸（NMDA）受体亚单位（NR 2A）、脑源性神经营养因子（BDNF）和Ras相关蛋白（RAB 3A）的表达。与此相反，同时给予LFS/DCS下调BDNF和RAB 3A的表达。我们的研究结果表明，LFS和DCS刺激可以调节网络成熟的兴奋性和同步性后，急性给药的抑制剂量的L-谷氨酸，上调NR 2A，BDNF和RAB 3A基因的表达。我们的研究也为研究电刺激对创伤性脑损伤后神经元反应和网络形成与修复的影响提供了一个新的框架。
Functional electrical stimulation (FES) is rapidly gaining traction as a therapeutic tool for mediating the repair and recovery of the injured central nervous system (CNS). However, the underlying mechanisms and impact of these stimulation paradigms at a molecular, cellular and network level remain largely unknown. In this study, we used embryonic stem cell (ESC)-derived neuron and glial co-cultures to investigate network maturation following acute administration of L-glutamate, which is a known mediator of excitotoxicity following CNS injury. We then modulated network maturation using chronic low frequency stimulation (LFS) and direct current stimulation (DCS) protocols. We demonstrated that L-glutamate impaired the rate of maturation of ESC-derived neurons and glia immediately and over a week following acute treatment. The administration of chronic LFS and DCS protocols individually following L-glutamate infusion significantly promoted the excitability of neurons as well as network synchrony, while the combination of LFS/DCS did not. qRT-PCR analysis revealed that LFS and DCS alone significantly up-regulated the expression of excitability and plasticity-related transcripts encoding N-methyl-D-aspartate (NMDA) receptor subunit (NR2A), brain-derived neurotrophic factor (BDNF) and Ras-related protein (RAB3A). In contrast, the simultaneous administration of LFS/DCS down-regulated BDNF and RAB3A expression. Our results demonstrate that LFS and DCS stimulation can modulate network maturation excitability and synchrony following the acute administration of an inhibitory dose of L-glutamate, and upregulate NR2A, BDNF and RAB3A gene expression. Our study also provides a novel framework for investigating the effects of electrical stimulation on neuronal responses and network formation and repair after traumatic brain injury.
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影响因子：
7.7
作者：
Brunoni, Andre Russowsky;Nitsche, Michael A.;Bolognini, Nadia;Bikson, Marom;Wagner, Tim;Merabet, Lotfi;Edwards, Dylan J.;Valero-Cabre, Antoni;Rotenberg, Alexander;Pascual-Leone, Alvaro;Ferrucci, Roberta;Priori, Alberto;Boggio, Paulo Sergio;Fregni, Felipe
通讯作者：
Fregni, Felipe
影响因子：
2.1
作者：
Demirtas-Tatlidede, Asli;Gurvit, Hakan;Emre, Murat
通讯作者：
Emre, Murat
影响因子：
3.2
作者：
Bakkum DJ;Radivojevic M;Frey U;Franke F;Hierlemann A;Takahashi H
通讯作者：
Takahashi H
影响因子：
2.4
作者：
GINZBURG, I;SOMPOLINSKY, H
通讯作者：
SOMPOLINSKY, H
影响因子：
2.5
作者：
Fee, MS;Mitra, PP;Kleinfeld, D
通讯作者：
Kleinfeld, D