Alterations of NMDA receptor subunits NR1, NR2A and NR2B mRNA expression and their relationship to apoptosis following transient forebrain ischemia
Alterations of NMDA receptor subunits NR1, NR2A and NR2B mRNA expression and their relationship to apoptosis following transient forebrain ischemia
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短暂性前脑缺血后 NMDA 受体亚基 NR1、NR2A 和 NR2B mRNA 表达的变化及其与细胞凋亡的关系
DOI：
10.1016/j.brainres.2010.09.035
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发表时间：
2010-11-18
期刊：
影响因子：
2.9
通讯作者：
Peng, Yuwen
中科院分区：
文献类型：
--
作者：
Liu, Zhian;Zhao, Weiwei;Peng, Yuwen
NMDA受体激活介导的谷氨酸兴奋性毒性在缺血性脑损伤的多个方面发挥着关键作用，但NMDA受体亚基NR1、NR2A和NR2B mRNA的表达及其与细胞凋亡的关系仍不清楚。本研究采用原位杂交和TUNEL染色技术研究短暂性前脑缺血后大鼠海马NMDA受体亚基mRNA的表达和细胞凋亡。结果显示，在CA1区，缺血再灌注（IR）后NR1 mRNA表达显着增加，在IR 24 h达到峰值，然后逐渐下降，直至IR 7 d。 NR2A和NR2B mRNA表达分别在IR 6 h和IR 12 h时降至最低水平，然后开始恢复。然后，NR2A 和 NR2B 的 mRNA 表达在 IR 48 小时时增加至峰值水平，随后持续下降，直到 IR 7 天。在CA3区和齿状回，mRNA表达的变异范围逐渐显着减小。 IR 24h时，主要在CA1区观察到凋亡阳性细胞。凋亡阳性细胞的数量持续增长，并在IR 48 h时急剧增加，并在IR 72 h时达到峰值。然后，凋亡阳性细胞的数量开始减少，但在IR 7天时，凋亡阳性细胞仍然存在。这些结果表明NMDA受体亚基mRNA表达的改变可能有助于短暂前脑缺血后海马的缺血性凋亡。 (C) 2010 Elsevier B.V. 保留所有权利。
Glutamate excitotoxicity mediated by NMDA receptor activation plays a key role in many aspects of ischemic brain injury, but the expression of NMDA receptor subunits NR1, NR2A and NR2B mRNA and their relationship to apoptosis is still unclear. In this study, we applied in situ hybridization and TUNEL staining to investigate the expression of NMDA receptor subunit mRNA and apoptosis in hippocampus of rats after transient forebrain ischemia. The results showed that in the CA1 region, NR1 mRNA expression was significantly increased following ischemia-reperfusion (IR), reaching peak levels at IR 24 h, and then gradually decreasing until IR 7 days. NR2A and NR2B mRNA expression dropped to lowest levels at IR 6 h and IR 12 h, respectively, and then started to recover. The mRNA expression of both NR2A and NR2B then increased to peak levels at IR 48 h, followed by a sustained decline until IR 7 days. In the CA3 region and dentate gyrus the range of variation in mRNA expression was significantly reduced gradually. At IR 24h, apoptosis-positive cells were observed mainly in the CA1 region. The number of apoptosis-positive cells continuously grew and showed a dramatic increase at IR 48 h and peaked at IR 72 h. Then, the number of apoptosis-positive cells started to decrease, but at IR 7 days the apoptosis-positive cells still remained. These results indicate that the alterations of NMDA receptor subunit mRNA expression may contribute to the ischemic apoptosis of hippocampus after transient forebrain ischemia. (C) 2010 Elsevier B.V. All rights reserved.