【摘要】 目的探讨慢性复合应激对大鼠学习与记忆的影响和cAMP/PKA-CREB信号系统在此机制中的作用。方法将成年雄性Wistar大鼠分为对照组:不作任何处理;慢性单一应激组:每天捆绑6 h,持续6周;慢性复合应激组:每天随机暴露于4种应激原中,持续6周。应激结束后,用Morris水迷宫(MWM)测试大鼠空间学习与记忆成绩;免疫组织化学方法观察大鼠海马PKA-Cβ和磷酸化的CREB的表达水平;应用RT-PCR法半定量检测海马组织内BDNF和Bcl-2的mRNAs水平。结果应激后在MWM寻找平台潜伏期,与对照组(18.9±13.0)s相比,慢性复合应激组(14.2±5.8)s明显缩短(P<0.05),显示其空间记忆明显增强,而慢性单一应激组(20.4±12.8)s无明显差异(P>0.05);慢性复合应激组大鼠海马CA1和CA3区PKA-Cβ的表达以及CA1区和齿状回pCREB的表达明显上调(P<0.05);而慢性单一应激组海马各亚区PKA-Cβ和pCREB的表达无显著性改变(P>0.05)。BDNF和Bcl-2mRNAs的表达水平3组间差别无显著性(P>0.05)。结论慢性复合应激可增强海马依赖的学习与记忆功能,多元的环境刺激可能是其增强的主要原因。PKA-CREB信号通路在其影响机制中发挥了一定的作用。更多还原

【Abstract】 Objective The present study is to explore the effect of the chronic multiple-stress on learning and memory of rats and the role of cAMP/PKA-CREB pathway in its mechanism. Methods Adult male Wistar rats were randomly divided into 3 groups: the control rats were housed in normal situations without any treatment;the chronically single-stressed rats were exposed to restraint stress 6 hours a day for 6 weeks;the chronically multiple-stressed rats were irregularly and alternatively subjected to 4 stressors for 6 weeks.After the stress experiment,all rats were tested for spatial learning and memory in Morris water maze(MWM).The expression of PKA-C_β and pCREB in different subfields of the hippocampus was assayed by using immunohistochemistry and the level of BDNF and Bcl-2 mRNAs in hippocampal tissues was determined by RT-PCR. Results The latency to escape from water in MWM after stress,as compared with control(18.9+13.0)s,the latency to escape of the chronically multiple-stressed(14.2+5.8)s was shorten significantly(P<0.05),indicating enhanced the spatial memory,while no apparent changes were observed in single-stressed(20.4+12.8)s(P>0.05).Compared with control,the expression of PKA-C_β in hippocampal area CA1 and CA3 and the expression of pCREB in area CA1 and dentate gyrus(DG) were distinctively higher in multiple-stressed rats(P<0.05),while no significant difference of the expression was discovered in single-stressed rats(P>0.05).No obvious difference was observed in the expression of hippocampal BDNF and Bcl-2 mRNAs among the 3 groups(P>0.05).Conclusion These results indicate that chronic multiple stress can enhance the hippocampus-dependent spatial learning and memory function.The stimulation of enriched environment may be the two major factors that lead to this enhancement,and cAMP/PKA-CREB signalling cascade may play a role in the mechanism of the enhanced performance.更多还原