孕期氯氮平暴露提高子代大鼠空间学习记忆能力并促进海马MAPK42磷酸化  

The gestational exposure in rats to clozapine promotes the spatial learning and memory and increases the phosphorylation of MAPK42 in the hippocampus of the adult offspring

作　　者：曾海燕 马光瑜[2] 崔立谦[3] 唐昭[3] 王文强 

机构地区：[1]厦门市仙岳医院康复科,厦门361014 [2]汕头大学医学院精神卫生中心,汕头515065 [3]汕头大学医学院药理学教研室,汕头515041

出　　处：《转化医学研究（电子版）》2014年第4期81-87,共7页Translational Medicine Research(Electronic Edition)

摘　　要：目的检测孕期氯氮平暴露对子代大鼠学习记忆行为的影响并探讨其机制。方法在妊娠中期(G6-15 d)的大鼠,每天腹腔注射氯氮平(10 mg/kg)。子代中的雄性成长至8周龄时接受Morris水迷宫试验,测试其空间学习记忆能力。然后处死动物,分离出海马和前额叶,采用Western-blot技术检测总MAPK及磷酸化MAPK的水平,应用RT-PCR技术检测zif268基因表达。结果有孕期氯氮平暴露史的子代大鼠空间记忆的获取、再认、和巩固均较对照表现更好。它们的海马部位MAPK42的磷酸化水平较对照组显著升高,但是其他指标两组间无差别。结论上述结果提示海马组织MAPK42的磷酸化可能在孕期氯氮平暴露导致的子代大鼠空间学习记忆提高中起重要作用。Objective The aim of this study was to examine the effect of gestational exposure to the antipsychotic clozapine in rats on the spatial learning and memory of adult offspring and to explore the underlying mechanism.Method During the middle period（G6- 15） of gestation,pregnant female rats received intraperitoneal injection of clozapine（10 mg/kg） once a day.When growing into 8-week old,the males of the offspring were subjected to Morris water maze test to measure their spatial learning and memory.Their brain tissue was processed for Westem-blot analysis to assess levels of MAPK44/42 and phosphorylated MAPK44/42,and real-time PCR to evaluate the expression of zif 268 gene.Result The offspring with the history of prenatal exposure to clozapine showed better performance in the Morris water maze compared with the controls.Western-blot analysis showed a significant higher level of p-MAPK 42 in the hippocampus of rats in the clozapine group,whereas no difference was found between the two groups in terms of the other indices.Conclusion These results suggest an important role of the MAPK42 phosphorylation in the promotion of the spatial learning and memory of adult offspring by clozapine given to pregnant female rats during the middle period of gestation.

关 键 词：孕期氯氮平暴露 空间学习记忆 海马 MAPK磷酸化 

分 类 号：R749.3[医药卫生—神经病学与精神病学]