Alterations in AMPA receptor subunit expression after experimental spinal cord contusion injury
Alterations in AMPA receptor subunit expression after experimental spinal cord contusion injury
复制标题
DOI：
10.1523/jneurosci.19-14-05711.1999
复制
发表时间：
1999-07-15
影响因子：
5.3
通讯作者：
Wrathall, JR
中科院分区：
文献类型：
--
作者：
Grossman, SD;Wolfe, BB;Wrathall, JR
嗜离子性谷氨酸受体（GluRs）的ampa偏好亚型是一种异聚寡聚离子通道，由四个亚基GluR1、GluR2、GluR3和GluR4的不同组合组装而成。这些受体的拮抗剂可以减轻实验性脊髓损伤（SCI）的影响，表明这些受体在脊髓损伤后的病理生理中发挥重要作用。我们利用大鼠挫伤性脊髓损伤的标准胸部减重模型，验证了脊髓损伤改变AMPA受体表达的假设。在脊髓损伤后24小时和1个月用定量Western blot和原位杂交检测AMPA受体亚基表达。损伤后24小时，GluR2蛋白水平在损伤部位附近优先降低。这种减少持续了1个月。在细胞水平上，毗邻损伤部位和远端损伤部位的腹侧运动神经元中GluR2和GluR4 mRNA均显著降低，而其他AMPA亚基mRNA维持在控制水平。相反，只有GluR1 mRNA在中外侧角交感神经节前神经元中表达降低。这些结果表明，神经元AMPA受体组成的群体特异性和持久性变化可能改变脊髓损伤后对谷氨酸的反应。这些改变可能不仅导致损伤的急性神经病理后果，而且也可能部分导致脊髓损伤后长期保存组织功能状态的改变。
The AMPA-preferring subtype of ionotropic glutamate receptors (GluRs) is a hetero-oligomeric ion channel assembled from various combinations of four subunits: GluR1, GluR2, GluR3, and GluR4. Antagonists of these receptors can mitigate the effects of experimental spinal cord injury (SCI), indicating that these receptors play a significant role in pathophysiology after spinal trauma. We tested the hypothesis that SCI alters expression of AMPA receptors using a standardized thoracic weight-drop model of rat contusive spinal cord injury. AMPA receptor subunit expression was measured at 24 hr and at 1 month after SCI with quantitative Western blot analysis and in situ hybridization. GluR2 protein levels were preferentially reduced near the injury site 24 hr after SCI. This reduction persisted at 1 month. At a cellular level, a significant decrease in both GluR2 and GluR4 mRNA was found in spared ventral motor neurons adjacent to the injury site and distal to it, with other AMPA subunit mRNAs maintained at control levels. In contrast, only GluR1 mRNA was decreased in the sympathetic preganglionic neurons of the intermediolateral horn. These results suggest population-specific and long-lasting changes in neuronal AMPA receptor composition, which may alter response to glutamate after SCI. These alterations may contribute not only to acute neuropathological consequences of injury, but they may also be partially responsible for the altered functional state of preserved tissue seen chronically after SCI.