Li Xiao-Heng, Liu Neng-Bao, Zhang Min-Hai, Zhou Yan-Ling, Liao Jia-Wan, Liu Xiang-Qian, Chen Hong-Wei
Department of Histology and Embryology, Tongji Medical School of Huazhong University of Science and Technology, Wuhan, China.
Chin Med J (Engl). 2007 Apr 20;120(8):669-74.
The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats.
Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze (MWM). The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique.
The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively. The performance of spatial learning and memory of rats was increased in chronic multiple stressed group (P < 0.05). The levels of Fyn, BDNF and TrkB proteins in the stressed group were higher than those of the control group (P < 0.05). The results of immunoreactivity showed that Fyn was present in the CA3 region of the hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated that level of Fyn mRNA was also upregulated in the hippocampus of the stressed group (P < 0.05).
Chronic multiple stress can enhance spatial learning and memory function of rats. The expression of Fyn, BDNF and TrkB proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus. These suggest that Fyn and BDNF/TrkB signal transduction pathways may participate in the process of the enhanced learning and memory during chronic multiple stress.
慢性应激对认知功能的影响一直是神经科学领域的热点话题之一。但其机制存在诸多争议。本研究旨在探讨慢性多重应激对大鼠空间学习记忆以及海马中Fyn、脑源性神经营养因子（BDNF）和酪氨酸激酶受体B（TrkB）表达的影响。
将成年大鼠随机分为对照组和慢性多重应激组。多重应激组大鼠每天接受垂直旋转、剥夺睡眠和束缚刺激，每天6小时，持续6周，夜间照明持续6周。在慢性多重应激前后，使用莫里斯水迷宫（MWM）测量所有大鼠的空间学习记忆能力。采用蛋白质免疫印迹法和免疫组织化学方法检测海马中Fyn、BDNF和TrkB蛋白的表达。用逆转录聚合酶链反应（RT-PCR）技术检测大鼠海马中Fyn和TrkB mRNA的水平。
对照组和应激组的逃避潜伏期分别为15.63秒和8.27秒。慢性多重应激组大鼠的空间学习记忆能力增强（P<0.05）。应激组中Fyn、BDNF和TrkB蛋白水平高于对照组（P<0.05）。免疫反应结果显示，Fyn存在于海马CA3区，BDNF阳性颗粒分布于CA1和CA3锥体细胞的细胞核以及齿状回颗粒细胞中。定量分析表明，应激组大鼠海马中Fyn mRNA水平也上调（P<0.05）。
慢性多重应激可增强大鼠的空间学习记忆功能。应激大鼠海马中Fyn、BDNF和TrkB蛋白表达及Fyn mRNA水平升高。这表明Fyn和BDNF/TrkB信号转导通路可能参与慢性多重应激期间学习记忆增强的过程。
