慢性复合应激对学习记忆的影响及cAMP/PKA-CREB信号通路的作用

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。

Effect of Chronic Multiple Stress on Learning and Memory of the Rats and the Role of cAMP/PKA CREB in its Mechanism

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 str essed 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-CSUB>β/SUB> 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-Cβ 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 mu