慢性复合应激对大鼠学习和记忆功能及海马内PKA-C_β表达的影响

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目的研究慢性复合应激对成年雄性大鼠学习记忆功能和海马内蛋白激酶A(PKACβ)表达的影响。方法将成年雄性Wistar大鼠随机分为对照组和应激组,应激组动物每天交替暴露于复合应激原中达6周,并测定应激第3周和第6周时两组动物的血清皮质酮水平。应激结束后,用Morris水迷宫和Y迷宫测试大鼠空间学习记忆成绩,并采用免疫组织化学方法分析海马各亚区PKACβ的表达。结果应激组大鼠的血清皮质酮水平在第3周明显高于对照组,但在第6周两组差别不明显。在Morris水迷宫测试中,应激组动物寻找隐蔽平台的潜伏期明显短于对照组;Y迷宫测试中,应激组动物寻找安全区的正确率也显著高于对照组。应激组大鼠的海马CA1和CA3区PKACβ的表达水平较对照组明显上调,而齿状回(DG)内PKACβ的表达在两组中无明显差别。结论慢性复合应激可增强大鼠海马依赖的学习记忆能力,PKA可能参与了其增强机制。 Objective To investigate the effects of chronic multiple stress on learning and memory abilities and protein kinase A (PKACβ) expression in hippocampus of adult male rats. Methods Adult male Wistar rats were randomly divided into control group and stress group. Animals in stress group were alternately exposed to compound stress for 6 weeks daily, and animals in both groups were measured at 3 weeks and 6 weeks Serum corticosterone levels. At the end of stress, the spatial learning and memory scores of rats were measured by Morris water maze and Y maze, and the expression of PKACβ in each subfield of hippocampus was analyzed by immunohistochemistry. Results The level of serum corticosterone in stress group was significantly higher than that in control group in the third week, but the difference was not obvious in the sixth week. In the Morris water maze test, the latent period of looking for a hidden platform in the stress group was significantly shorter than that in the control group. In the Y maze test, the correct rate of looking for a safe area in the stressed group was also significantly higher than that of the control group. The expression level of PKACβ in hippocampal CA1 and CA3 of rats in stress group was significantly higher than that in control group, while the expression of PKACβ in dentate gyrus (DG) showed no significant difference between the two groups. Conclusion Chronic stress can enhance hippocampus-dependent learning and memory in rats. PKA may be involved in its mechanism of enhancement.
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