听源性惊厥刺激使P77PMC大鼠脑内NR2A/2B基因表达下调

Down regulation of NMDA receptor subunits NR2A and NR2B mRNA expression after audiogenic seizure in epilepsy prone rat brain

目的 :研究遗传性癫疒间 易感大鼠P77PMC惊厥后脑内N 甲基 D 门冬氨酸 (N methl D aspartate ,NMDA)NMDA受体亚基NR2A及NR2BmRNA表达情况。方法 :以原位杂交技术研究P77PMC大鼠在听源性惊厥刺激后不同时间脑内不同脑区NR2A及NR2BmRNA表达。结果 :惊厥后NR2AmRNA表达在P77PMC大鼠大脑运动、感觉皮层 ,海马CA1、CA2、CA3区和齿状回均呈时间依赖性下调。惊厥后 30minNR2AmRNA表达即出现下降 ,惊厥后 2hmRNA水平降至最低 ,4～ 8h后恢复到基础水平 ,2 4h再次低于基础水平。惊厥后 8h内上述脑区NR2BmRNA表达规律与NR2A基本相同。结论 :P77PMC大鼠在发生听源性惊厥后脑内NR2A及NR2BmRNA表达出现下调 ,这可能影响随后的NR2A、NR2B的蛋白表达 ,从而导致惊厥后脑内NMDA受体的亚基组成发生改变 。

To study the expression of N methl D aspartate (NMDA) receptor subunits NR2A and NR2B mRNA after audiogenic seizure in the brain of genetically epilepsy prone rats P77PMC. Methods: In situ hybridization technique was used to study the mRNA expression of NR2A and NR2B at different times after audiogenic seizure in different brain areas of P77PMC rats. Results: The NR2A mRNA expression showed time dependent down regulation in cerebral motor and sensory cortex, hippocampus CA1 CA3, dentate gyrus after audiogenic seizure. Down regulation emerged 30 min after seizure, 2 hours later the mRNA reached the lowest level, 4 8 hours later returned to the baseline, and 24 hours later decreased lower than baseline again. The mRNA expression of NR2B was quite similar to that of the NR2A after seizure. Conclusion: The down regulation of NR2A and NR2B mRNA indicates that the subunit composition of the NMDA receptor complexes may be altered after audiogenic seizure. These structural alterations could make the function of NMDA receptor complexes change and subsequently influence the excitability of brain as well as the susceptibility of epilepsy.