Lou Yan, Wang Wei-ping, Li Pan, Duan Rui-sheng, Pei Lin
Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang 050050, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Nov;38(6):949-53.
The changes of transcription factors CREB and glutamate receptor N-methyl-D-aspartate (NMDA) receptor subtype NR1 expressing in hippocampus and the relationship between CREB or NR1 expression change and learning or memory deficit after epilepsy. Exploring the role of CREB and NR1 in impairment of cognitive function after epilepsy.
Status epilepticus (SE) and chronic epilepsy (CEP) rats were kindled by using pentylenetetrazol (PTZ) as the convulsant. The function changes of learning and memory in different types of epileptic model rats were examined by alternative electro-stimulus Y-maze test. RT-PCR detection was used to analyze NR1 and CREB mRNA expression in hippocampus tissues. Immunocytochemistry technique was used to analyze CREB protein (pCREB) expression in hippocampus tissue.
The results of alternative electro-stimulus Y-maze test (AESYT) showed that the total error (TE) in SE rats were higher than corresponding control rats at 1 d and 10 d after epilepsy (P < 0.05), there were no difference at 30 d after epilepsy (P > 0.05); In CEP rats, the TE in AESYT were higher than corresponding control rats at 1 d, 10 d and 30 d after epilepsy (P < 0.05). It was showed that expression of NR1 mRNA in hippocampus was significantly decreased in SE group and CEP group (P < 0.05) comparing with corresponding control group at 24 h after epilepsy, there were no significant difference between any two groups at 30 d after epilepsy (P > 0.05). The expression of CREB mRNA in hippocampus was significantly decreased in SE group (P < 0.05) at 24 h after epilepsy, and there was no significant difference in CEP group. At 30 d after epilepsy, the expression of CREB mRNA was decreased only in CEP group, but no difference in SE group. It was observed that pCREB positive neurons were distributed in CA1, CA3 and DG of rat hippocampus. The expression of pCREB positive cellular nucleus significantly decreased in SE group and CEP group comparing with control group at 24 h after epilepsy.
The change of learning and memory after epilepsy is related to the expression of NR1 and CREB in hippocampus. The epilepsy seizures to SE and CEP rats could result in the impairment of learning and memory, and be followed by the decreases in expression of NR1 and CREB mRNA and level of CREB protein. It shows that NR1 and CREB may be involved in the pathophysiological process of learning and memory deficit.
探讨癫痫后海马中转录因子环磷腺苷效应元件结合蛋白（CREB）和谷氨酸受体N-甲基-D-天冬氨酸（NMDA）受体亚型NR1表达的变化，以及CREB或NR1表达变化与学习记忆障碍之间的关系。探究CREB和NR1在癫痫后认知功能损害中的作用。
采用戊四氮（PTZ）点燃制作癫痫持续状态（SE）和慢性癫痫（CEP）大鼠模型。通过交替电刺激Y迷宫试验检测不同类型癫痫模型大鼠学习记忆功能的变化。采用逆转录-聚合酶链反应（RT-PCR）检测海马组织中NR1和CREB mRNA的表达。采用免疫细胞化学技术分析海马组织中CREB蛋白（pCREB）的表达。
交替电刺激Y迷宫试验结果显示，SE大鼠在癫痫发作后1 d和10 d时总错误次数（TE）高于相应对照组（P < 0.05），癫痫发作后30 d时无差异（P > 0.05）；CEP大鼠在癫痫发作后1 d、10 d和30 d时AESYT中的TE均高于相应对照组（P < 0.05）。结果表明，与相应对照组相比，SE组和CEP组大鼠在癫痫发作后24 h时海马中NR1 mRNA表达显著降低（P < 0.05），癫痫发作后30 d时各组间无显著差异（P > 0.05）。SE组大鼠在癫痫发作后24 h时海马中CREB mRNA表达显著降低（P < 0.05），CEP组无显著差异。癫痫发作后30 d时，仅CEP组CREB mRNA表达降低，SE组无差异。观察到pCREB阳性神经元分布于大鼠海马的CA1、CA3和齿状回（DG）。癫痫发作后24 h时，SE组和CEP组pCREB阳性细胞核的表达与对照组相比显著降低。
癫痫后学习记忆的改变与海马中NR1和CREB的表达有关。癫痫发作导致SE和CEP大鼠学习记忆功能受损，随后NR1和CREB mRNA表达及CREB蛋白水平降低。表明NR1和CREB可能参与了学习记忆障碍的病理生理过程。
