Transient global ischemia in rat brain promotes different NMDA receptor regulation depending on the brain structure studied
Transient global ischemia in rat brain promotes different NMDA receptor regulation depending on the brain structure studied
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DOI：
10.1016/j.neuint.2008.09.016
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发表时间：
2009-03-01
影响因子：
4.2
通讯作者：
Fernandez-Lopez, Arsenio
中科院分区：
文献类型：
--
作者：
Dos-Anjos, Severiano;Martinez-Villayandre, Beatriz;Fernandez-Lopez, Arsenio
本实验研究了大鼠脑缺血再灌注损伤后N-甲基-D-天冬氨酸受体主要亚基（NR 1、NR 2A和NR 2B）在不同易损性结构中的mRNA表达。该研究使用定量实时PCR对来自3个月大的雄性Sprague-Dawley大鼠的样品进行，所述大鼠在全脑短暂前脑缺血之后再灌注48小时。与假手术组相比，损伤组动物的所有结构中NMDA受体亚基mRNA的表达均显著降低。海马亚区（CA 1，CA 3和齿状回）以及尾壳核，都报告是高度缺血脆弱的结构，表现出显着较低的NMDA受体亚单位的mRNA水平比大脑皮层，这被认为是一个更缺血抵抗结构。分析不同亚基的mRNA水平的比率作为所研究的每个结构的NMDA受体表达模式的量度。海马区的NMDA受体表达的变化后，侮辱，与NR 1和NR 2B亚基的NR 2A显着减少。因此，在假手术动物中观察到的NR 1：NR 2A：NR 2B（1：1：2）比率在受侮辱动物中变为（2：1：4）。这种修改后的表达模式是相似的，在CA 1，CA 3和齿状回，尽管这些海马区报道的不同的脆弱性。与此相反，在尾壳核或大脑皮层的表达模式没有观察到显着差异比较假手术动物与缺血再灌注大鼠。我们的研究结果支持这一观点，即NMDA受体基因表达的调节依赖于大脑结构，而不是在研究区域的更高或更低的脆弱性。(C)2008爱思唯尔有限公司保留所有权利。
The mRNA expression of the major subunits of N-methyl-D-aspartate receptors (NR1, NR2A and NR2B) following ischemia-reperfusion was studied in structures with different vulnerabilities to ischemic insult in the rat brain. The study was performed using quantitative real-time PCR on samples from 3-month-old male Sprague-Dawley rats after global transient forebrain ischemia followed by 48 h of reperfusion. Expression of NMDA receptor subunits mRNAs decreased significantly in all structures studied in the injured animals as compared to the sham-operated ones. The hippocampal subfields (CA1, CA3 and dentate gyrus) as well as the caudate-putamen, both reported to be highly ischemic-vulnerable structures, showed outstandingly lower mRNA levels of NMDA receptor subunits than the cerebral cortex, which is considered a more ischemic-resistant structure. The ratios of the mRNA levels of the different subunits were analyzed as a measure of the NMDA receptor expression pattern for each structure studied. Hippocampal areas showed changes in NMDA receptor expression after the insult, with significant decreases in the NR2A with respect to the NR1 and NR2B subunits. Thus, the NR1:NR2A:NR2B (1:1:2) ratios observed in the sham-operated animals became (2:1:4) in insulted animals. This modified expression pattern was similar in CA1, CA3 and the dentate gyrus, in spite of the different vulnerabilities reported for these hippocampal areas. In contrast, no significant differences in the expression pattern were observed in the caudate-putamen or cerebral cortex on comparing the sham-operated animals with the ischemia-reperfused rats. Our results support the notion that the regulation of NMDA receptor gene expression is dependent on the brain structure rather than on the higher or lower vulnerability of the area studied. (C) 2008 Elsevier Ltd. All rights reserved.