匹罗卡品诱导的颞叶癫痫小鼠恐惧记忆行为学变化

Changes of fear conditioning in pilocarpine-induced temporal lobe epilepsy in mice

目的研究匹罗卡品(PILO)诱导的颞叶癫痫小鼠的恐惧记忆行为学变化规律,探讨此行为学检测评价颞叶癫痫的可行性。方法建立PILO小鼠癫痫模型,分PILO注射2周组(n=11)、PILO注射6周组(n=7)和PILO注射10周组(n=11),同时设正常对照组(n=10)。对各组小鼠进行场景恐惧记忆实验,同时进行海马Nissl染色观察。结果经过声音提示恐惧记忆训练,小鼠恐惧记忆的获得受到了损害。场景恐惧记忆测试发现PILO注射2周组小鼠的僵住时间与对照组无统计学差异(P>0.05),而6周组和10周组则显示明显的恐惧记忆减弱(P<0.05);声音提示的恐惧记忆测试发现PILO注射2周组和6周组小鼠僵住时间与对照组无统计学差异(P>0.05),而10周组则出现明显的恐惧记忆减弱(P<0.05)。Nissl染色显示,PILO注射6周和10周组小鼠海马CA3的锥体细胞脱失,排列稀疏,间隙增大,许多细胞胞质中的Nissl小体减少或消失。结论PILO诱导的颞叶癫痫小鼠恐惧记忆的形成及场景恐惧记忆的回忆都受到了损害,但声音提示的恐惧记忆得到了一定程度的保留。恐惧记忆行为学的变化可能会成为评价颞叶癫痫的一个临床指标。

Objective To investigate the changes of fear conditioning in pilocarpine （PILO）-induced temporal lobe epilepsy in mice and to analyze the feasibility of applying this behavioral test in evaluation of temporal lobe epilepsy. Methods Epilepsy models were induced by PILO in mice, and the animals were divided into four groups： two-week group （n=11）, two weeks after PILO injection; six-week group（ n = 7） , six weeks after PILO injection; ten-week group（n =11）, ten weeks after PILO injection; and normal control group（ n = 10）. Emotional learning and memory were assessed by fear-conditioning test, and the brains were processed for histological analysis. Results Compared with normal control group, the requirement of fear memory was impaired in the tone cued conditioning training. However, the cognitive function was significantly decreased in six-week group and ten-week group （P 〈 0.05） , while there was no significant decrease in the contextual test for two-week group （ P 〉 0.05）. Whereas only ten-week group was observed significant reduction in tone cued test （P 〈0.05）. Conclusion Processing of complex contextual stimuli is severely affected in PILO-induced temporal lobe epilepsy, whereas conditioning to simple tone cues is better preserved. Changes of fear conditioning may be a clinical indicator to assess the temporal lobe epilepsy.