Sun Chen-you, Qi Shuang-shuang, Lou Xin-fa, Sun Shu-hong, Wang Xin, Dai Kai-yu, Hu Si-wang, Liu Neng-bao
Department of Anatomy, Wenzhou Medical College, Wenzhou 325035, China.
Chin Med J (Engl). 2006 Jan 20;119(2):140-7.
The effect of chronic stress on cognitive functions has been one of the hot topic in neuroscience. But there has been much controversy over its mechanism. Such single stressor applied in the past could not simulate complicated living circumstances that people confronted with. The aim of this study was to investigate the effects of chronic multiple-stress on learning and memory as well as on the levels of calcium/calmodulin-dependent protein kinase II (CaMKII), calmodulin (CaM) mRNA, and cAMP-response element binding protein (CREB) mRNA in the hippocampus of rats.
The rats were divided randomly into stressed and control groups. The stressed group was given chronic multiple-stress for 6 weeks to set up a chronic multiple-stressed model. The rats' performance of spatial learning and memory was tested using Morris Water Maze (MWM) and Y-maze. Meanwhile, the expressions of CaMKII, CaM mRNA and CREB mRNA of rats' hippocampus were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. In addition, the width of synaptic cleft and the thickness of post-synaptic densities (PSD) were observed in the hippocampal CA3 region of rats by electron microscopy.
After exposure to chronic multiple-stress for 6 weeks, the ability of learning and memory of the stressed group was higher than that of the control group (P < 0.05, P < 0.01). The width of synaptic cleft was smaller and the thickness of PSD was larger in the hippocampal CA3 region of the stressed group than in that of the control group (P < 0.01). The CaMK II immunostaining of the stressed group was stronger than that of the control group in the stratum radiatum and oriens of the hippocampal CA1 and CA3, especially in the stratum oriens. Quantitative analysis indicated that the expression of CaMK II, CaM mRNA, and CREB mRNA in the hippocampus of the stressed group was higher than that of the control group (P < 0.05, P < 0.01).
The capacity of learning and memory can be enhanced after chronic multiple-stress. The increased levels of CaMK II, CaM mRNA, and CREB mRNA may contribute to the enhancing effect of chronic multiple-stress on learning and memory.
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。过去应用的单一应激源无法模拟人们所面临的复杂生活环境。本研究旨在探讨慢性多重应激对大鼠学习记忆以及海马中钙/钙调蛋白依赖性蛋白激酶II（CaMKII）、钙调蛋白（CaM）mRNA和环磷酸腺苷反应元件结合蛋白（CREB）mRNA水平的影响。
将大鼠随机分为应激组和对照组。应激组给予慢性多重应激6周以建立慢性多重应激模型。采用莫里斯水迷宫（MWM）和Y迷宫测试大鼠的空间学习记忆能力。同时，分别通过免疫组织化学、蛋白质印迹法和逆转录聚合酶链反应（RT-PCR）检测大鼠海马中CaMKII、CaM mRNA和CREB mRNA的表达。此外，通过电子显微镜观察大鼠海马CA3区突触间隙宽度和突触后致密物（PSD）厚度。
慢性多重应激6周后，应激组的学习记忆能力高于对照组（P < 0.05，P < 0.01）。应激组海马CA3区突触间隙宽度小于对照组，PSD厚度大于对照组（P < 0.01）。应激组海马CA1和CA3区辐射层和原层，尤其是原层的CaMK II免疫染色强于对照组。定量分析表明，应激组海马中CaMK II、CaM mRNA和CREB mRNA的表达高于对照组（P < 0.05，P < 0.01）。
慢性多重应激后学习记忆能力可增强。CaMK II、CaM mRNA和CREB mRNA水平的升高可能有助于慢性多重应激对学习记忆的增强作用。
