条件性恐惧消退与海马突触素、神经细胞黏附分子免疫反应阳性物质的动态变化

目的 研究条件性恐惧消退过程中消退记忆保持成绩与海马神经细胞黏附分子(NCAM)、突触索的动态变化.方法 成年雄性SD大鼠72只,随机分为自然消退组、立即消退组和24h后消退组.采用声音结合强烈足底电击建立大鼠条件性恐惧模型.两消退训练组分别于建模后15 min和24 h进行消退训练.在消退后不同时间(第1,3,7和20天)测定各组大鼠消退保持成绩,并用免疫组织化学法检测不同时间点大鼠海马内突触素、NCAM的表达,结合图像分析技术对各组大鼠海马突触素、NCAM进行校正光密度(COD)测定.结果 ①消退保持成绩整体呈逐渐增加的趋势:与自然消退组比,24h后消退组消退保持成绩较好,立即消退组早期较差,远期效果略好于自然消退组.②在消退后早期,大鼠海马突触素与NCAM免疫反应阳性物质平均光密度值短期内迅速增加,第3天最高,以后呈下降趋势.24h后消退组在消退后第1,3,7和20天突触素[COD值均值分别为(0.0140±0.0088),(0.0345±0.0076),(0.0277±0.0067),(0.0112±0.0031),P<0.01]、NCAM[COD值分别为(0.0235±0.0084),(0.0613±0.0057),(0.0515±0.0115),(0.0249±0.0115),P<0.05或P<0.01]表达高于自然消退组;立即消退组突触素、NCAM表达也高于自然消退组,但差异无显著性.结论 暴露治疗可以通过提高海马内突触素与NCAM的含量而降低恐惧记忆、促进恐惧消退,但在条件性恐惧建立后不同的时间实施暴露治疗效果不同.

Changes of synaptophysin and neural cell adhesion molecule immunopositive substances in hippocampus after fear extinction

Objective To study the changes of synaptophysin and neural cell adhesion molecule (NCAM)immunopositive substances in hippocampus after fear extinction.Methods 72 male adult SD rats were randomly divided into natural extinction group,immediate extinction group and 24-hour extinction group.Conditinned fear animal model of rats was established by tone paired foot shock.Fear extinction was trained in 15 minutes or 24-hours after establishment of fear memory.Extinction retention test and immunohistochemistry of synaptophysin and NCAM of hippocampus were done at 1 st,3rd,7th and 20th days after fear extinction.The corrected optical density of the positive synaptophysin and NCAM staining in the hippocampus was measured by the computer natural extinction group,24-hour extinction group was better,it was shorter during the early stage after fear extinction,synaptophysin and NCAM immunopositive substances in hippocampus were increased quickly and reached the highest at 3rd day then decreased for all groups.Synaptophysin and NCAM expressed obviously in 24-hour extinction group at different time after fear extinction,the expression of synaptophysin(0.0140±0.0088,0.0345±0.0076,0.0277±0.0067,0.0112±0.0031,P＜0.01),NCAM(0.0235±0.0084,0.0613±0.0057,0.0515±0.0115.0.0249±0.0115,P＜0.05 or P＜0.01)in hippocampus in rats of 24 hour extinction group were higher than those in natural extinction group.Synaptophysin and NCAM expressed increase in immediate extinction group,but there were no significantly difference between immediate extinction group and natural extinction group.Conclusion Exposure therapy could decrease fear memory and might enhance fear extinction by increase the level of synaptophysin and NCAM in hippocampus,but exposure therapy given in different time show different therapeutic effeets.