Dos-Anjos Severiano, Martínez-Villayandre Beatriz, Montori Sheyla, Regueiro-Purriños Marta M, Gonzalo-Orden José M, Fernández-López Arsenio
Instituto de Biomedicina, Universidad de León, Spain.
Neurochem Int. 2009 Mar-Apr;54(3-4):180-5. doi: 10.1016/j.neuint.2008.09.016. Epub 2008 Dec 3.
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 48h 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.
在大鼠脑中，对缺血再灌注后N-甲基-D-天冬氨酸受体（NR1、NR2A和NR2B）主要亚基的mRNA表达进行了研究，研究对象为对缺血性损伤具有不同易损性的脑结构。该研究采用定量实时PCR技术，对3月龄雄性Sprague-Dawley大鼠进行全脑短暂性缺血再灌注48小时后的样本进行检测。与假手术组相比，损伤动物所有研究结构中NMDA受体亚基mRNA的表达均显著降低。海马亚区（CA1、CA3和齿状回）以及尾状核-壳核，均被报道为高度缺血易损结构，其NMDA受体亚基的mRNA水平显著低于被认为缺血耐受性更强的大脑皮层。分析不同亚基mRNA水平的比值，作为所研究每个结构中NMDA受体表达模式的一种衡量指标。海马区在损伤后NMDA受体表达发生变化，NR2A相对于NR1和NR2B亚基显著减少。因此，假手术动物中观察到的NR1:NR2A:NR2B（1:1:2）比值在损伤动物中变为（2:1:4）。尽管这些海马区报道的易损性不同，但这种改变的表达模式在CA1、CA3和齿状回中相似。相比之下，将假手术动物与缺血再灌注大鼠进行比较时，尾状核-壳核或大脑皮层的表达模式未观察到显著差异。我们的结果支持这样一种观点，即NMDA受体基因表达的调控取决于脑结构，而非所研究区域的易损性高低。
