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首页> 外文期刊>Journal of Neurophysiology >Stretch injury selectively enhances extrasynaptic, GluN2B-containing NMDA receptor function in cortical neurons
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Stretch injury selectively enhances extrasynaptic, GluN2B-containing NMDA receptor function in cortical neurons

机译:拉伸损伤选择性增强皮质神经元中突触外,含GluN2B的NMDA受体功能

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摘要

Alterations in the function and expression of NMDA receptors are observed after in vivo and in vitro traumatic brain injury. We recently reported that mechanical stretch injury in cortical neurons transiently increases the contribution of NMDA receptors to network activity and results in an increase in calcium-permeable AMPA (CP-AMPA) receptor-mediated transmission 4 h postinjury (Goforth et al. 2011). Here, we evaluated changes in the function of synaptic vs. extrasynaptic GluN2B-containing NMDA receptors after injury. We also determined whether postinjury treatment with the GluN2B-selective antagonist Ro 25-6981 or memantine prevents injury-induced increases in CP-AMPA receptor activity. We found that injury increased extrasynaptic, GluN2B-containing NMDA receptor-mediated whole cell currents. In contrast, we found no differences in synaptic NMDA receptor-mediated transmission after injury. Furthermore, treatment with Ro 25-6981 or memantine after injury prevented injury-induced increases in CP-AMPA receptor-mediated activity. Together, our data suggest that increased NMDA receptor activity after injury is predominantly due to alterations in extrasynaptic, GluN2B-containing NMDA receptors and that activation of these receptors may contribute to the appearance of CP-AMPA receptors after injury.
机译:在体内和体外脑外伤后观察到NMDA受体的功能和表达发生变化。我们最近报道,皮层神经元的机械性牵张性损伤会暂时增加NMDA受体对网络活动的贡献,并导致伤后4 h钙可渗透AMPA(CP-AMPA)受体介导的传递增加(Goforth et al。2011)。在这里,我们评估了损伤后突触与突触外含GluN2B的NMDA受体功能的变化。我们还确定了使用GluN2B选择性拮抗剂Ro 25-6981或美金刚胺进行的损伤后治疗是否可以防止损伤诱导的CP-AMPA受体活性增加。我们发现损伤增加了突触外,含GluN2B的NMDA受体介导的全细胞电流。相反,我们发现损伤后突触NMDA受体介导的传递没有差异。此外,损伤后用Ro 25-6981或美金刚治疗可防止损伤诱导的CP-AMPA受体介导的活性增加。总之,我们的数据表明,损伤后NMDA受体活性增加主要归因于突触外,含GluN2B的NMDA受体的改变,并且这些受体的活化可能有助于损伤后CP-AMPA受体的出现。

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