摘要
目的探讨核转录因子环磷腺苷反应元件结合蛋白(CREB)和兴奋性氨基酸NMDA受体亚型NR1在癫痫后学习记忆功能改变中的变化及意义。方法制备戊四氮点燃大鼠癫痫持续状态(Status epilepticus,SE)和慢性癫痫(chronic epilepsy,CEP)模型,采用交替电刺激Y迷宫试验动态观察大鼠癫痫后学习记忆功能变化。RT-PCR方法检测大鼠海马组织CREB和NR1 mRNA的表达,免疫组化染色观察大鼠海马磷酸化的CREB蛋白水平表达变化。结果SE大鼠致痫成功后24h交替电刺激Y迷宫试验错误次数增多(P<0.05),30d恢复正常。CEP大鼠24h和30d错误次数均有所增加(P<0.05)。同时伴有海马组织NR1 mRNA和CREB mRNA表达的下调(P<0.05)及磷酸化CREB蛋白水平表达量的下降(P<0.05)。结论海马组织NMDA受体和CREB的表达变化可能参与了癫痫大鼠学习记忆功能改变的病理生理过程。
Objective 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. Methods 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. Results 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, hut 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. Conclusion 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 he followed by the decreases in expression of NR1 and CREB mRNA and level of CREB protein. It shows that NR1 and CREB may he involved in the pathophysiological process of learning and memory deficit.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2007年第6期949-953,共5页
Journal of Sichuan University(Medical Sciences)
