Stretch injury selectively enhances extrasynaptic, GluN2B-containing NMDA receptor function in cortical neurons
Stretch injury selectively enhances extrasynaptic, GluN2B-containing NMDA receptor function in cortical neurons
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DOI：
10.1152/jn.01011.2012
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发表时间：
2013-07-01
影响因子：
2.5
通讯作者：
Goforth, Paulette B.
中科院分区：
文献类型：
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作者：
Ferrario, Carrie R.;Ndukwe, Blaise O.;Goforth, Paulette B.
体内和体外创伤性脑损伤后，观察NMDA受体功能和表达的变化。我们最近报道，大脑皮层神经元的机械性牵张损伤一过性地增加了NMDA受体对网络活动的贡献，并导致损伤后4小时钙通透性AMPA(CP-AMPA)受体介导的传递增加(Goforth等人)。2011年)。在这里，我们评估了损伤后突触和突触外含GluN2B的NMDA受体功能的变化。我们还确定了损伤后使用GluN2B选择性拮抗剂RO25-6981或美金刚是否能阻止损伤诱导的CP-AMPA受体活性的增加。我们发现，损伤增加了突触外，含有GluN2B的NMDA受体介导的全细胞电流。相反，我们没有发现损伤后突触NMDA受体介导的传递的差异。此外，损伤后用RO25-6981或美金刚治疗可阻止损伤诱导的CP-AMPA受体介导的活性增加。综上所述，我们的数据表明，损伤后NMDA受体活性的增加主要是由于含有GluN2B的突触外NMDA受体的变化，这些受体的激活可能有助于损伤后CP-AMPA受体的出现。
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.