发作间癎样放电致大鼠海马CaMKIV／CREB信号途径紊乱研究  

Interictal epileptiform discharges facilitate the dysfunction of CaMKIV and CREB signaling in hippocampus of rats

作　　者：王庆松[1] 林杭[1] 王伟文[1] 王俊[1] 郁可[1] 

机构地区：[1]成都军区总医院神经科,成都610083

出　　处：《中国行为医学科学》2008年第3期204-206,共3页Chinese Journal of Behavioral Medical Science

摘　　要：目的探讨癫痫性情感行为障碍与认知功能受损的神经生物学机制。方法在海马电点燃及发作间瘸样放电（IED）动物模型基础上，将64只Wistar大鼠随机分为IED、海马点燃、电极对照和正常对照4组（每组n=16）。采用蛋白质免疫印迹法动态观测实验动物海马Ca^2＋／CaM依赖性蛋白激酶IV（CaMKIV）与核转录因子cAMP反应元件结合蛋白（CREB）介导的核转录途径的变化规律。结果电点燃后1d，IED组与海马点燃组大鼠海马CaMKIV[2组A值分别为（2．97±0．88）和（3．06±0．92）]与CREB[（4．23±1．25）和（3．09±0．93）]、磷酸化CREB[pCREB，（3．39±0．97）和（2．92±0．86）]及CREB结合蛋白[CBP，（2．82±0．82）和（3．35±0．98）]表达均较电极对照及正常对照组增高[电极对照组CaMKIV、CREB、pCREB与CBP表达分别为（0．92±0．27）、（1．15±0．34）、（1．07±0．32）与（0．96±0．28）；正常对照组分别为（0．89±0．26）、（1．06±0．31）、（1．24±0．35）与（1．04±0．31）]，差异具有显著性（P〈0．01）。14d时IED组大鼠再次明显增高[CaMKIV、CREB、pCREB及CBP分别为（2．65±0．78）、（3．96±1．15）、（3．95±1．15）及（4．59±1．34）]，与海马点燃组及两对照组相比，差异具有显著性（P〈0．05）。结论IED所致海马CaMKIV／CREB信号途径较长时间的激活，在痫样放电引发的长时程情感行为异常与学习和记忆能力受损中可能有重要意义。Objective To explore the neurobiological basis involved in the pathogenesis of the epileptic emotionality and cognitive impairment. Methods 64 male Wistar rats were divided randomly into 4 groups. IED Group （ n = 16 ） for kindling with rapidly recurring hippocampal seizure followed by subconvulsive electrical stimu- lation to hippocampus 13 days later. HK Group （ n= 16） for hippocampal kindling. CE Group （ n= 16） for control of electrode implanted in hippocampus without stimulation, and NC Group （ n = 16） for normal control. The alterations of hippocampal Ca^2＋/CaM dependent kinase IV （CaMKIV） and cAMP response element-binding protein （CREB） mediated transcription pathway were investigated by Western blot analyses. Results The Western anal- ysis revealed that the expressions of hippocampal CaMKIV, CREB, phosphorylated CREB （pCREB） and CREB binding protein （CBP） in rats of IED group （2.97 ± 0. 88, 4.23 ± 1.25, 3.39 ± 0.97 and 2.82 ± 0.82 for CaMKIV, CREB, pCREB and CBP, respectively） or HK group （3.06 ± 0.92, 3.09 ± 0.93, 2.92 ± 0.86 and 3.35 ± 0.98 respectively） were markedly elevated at 1 day after kindling compared with CE Groups （0.92 ± 0.27,1.15±0.34,1.07±0.32 and 0.96±0.28 respectively） and NC group（0.89±0.26, 1.06±0.31, 1.24 ± 0.35 and 1.04 ± 0.31 respectively）. Moreover, the expressions of hippocampal CaMKIV, CREB, pCREB and CBP in IED Group （2.65 ± 0.78, 3.96 ± 1.15, 3.95 ± 1.15 and 4.59 ± 1.34 respectively） were still increased at day 14 after kindling compared with other three groups （ P 〈 0.05）. Conclusion The lasting dysfunction of CaMKIV/CREB signaling in the hippocampal formation of rats may play an important role in the long-term neuropsychological sequelae following epileptiform discharges.

关 键 词：瘸样放电 钙/钙调素依赖性蛋白激酶 CAMP反应元件结合蛋白 转录因子 认知 功能 

分 类 号：R742.1[医药卫生—神经病学与精神病学]