急慢性应激对小鼠自发行为和空间学习记忆功能的影响及其机制

发布时间：2018-07-06 18:20

本文选题：急性应激 + 慢性应激　；参考：《曲阜师范大学》2010年硕士论文

【摘要】： 本研究分别采用单因素急性应激动物模型(足底电击)和多因素慢性不可预知应激动物模型(拥挤、冷/热刺激、白噪声、高台、足底电击,28天),研究了急、慢性应激条件下小鼠自发行为和空间学习记忆能力的变化及其脑内c-fos表达的变化情况。旨在探讨不同应激条件对小鼠自发行为和空间学习记忆能力的影响及其作用机制。以开场实验检测小鼠新异环境下的自发行为；采用Morris水迷宫测试小鼠的空间学习记忆能力；以酶联免疫法测定小鼠血清皮质酮含量,通过HE染色观察小鼠海马、前脑皮层及下丘脑室旁核神经元的形态学变化；并运用免疫组织化学方法检测小鼠海马、前脑皮层和下丘脑室旁核的c-fos表达。研究结果如下： 1.急性应激后,与对照组小鼠比较,应激组小鼠的水平穿越格数、直立次数、粪便粒数均明显减少,中央格停留时间显著延长,但修饰次数无显著变化；慢性应激后,与对照组小鼠比较,应激组小鼠的水平穿越格数、直立次数、修饰次数均明显减少,中央格停留时间显著延长,粪便粒数明显增多。 2.急性应激后,与对照组小鼠比较,应激组小鼠寻找平台的逃避潜伏期明显缩短,且在空间搜索实验中,其在目标象限停留时间明显延长；慢性应激后,与对照组小鼠比较,应激组小鼠寻找平台的逃避潜伏期明显延长,且在空间搜索实验中,其在目标象限停留时间明显缩短。 3.急、慢性应激后,与对照组小鼠比较,应激组小鼠血清皮质酮含量均明显增加,但急性应激增加的程度更强。 4.急性应激后,与对照组小鼠比较,应激组小鼠的神经元形态结构没有明显变化；慢性应激后,与对照组小鼠比较,应激组小鼠海马、前脑皮层及下丘脑室旁核神经元数量明显减少,细胞萎缩变性,呈现不同程度的损伤现象。 5.急性应激后,与对照组小鼠比较,应激组小鼠海马、前脑皮层及下丘脑室旁核c-fos阳性细胞数明显增多,平均目标灰度值明显降低；慢性应激后,与对照组小鼠比较,应激组小鼠海马、前脑皮层及下丘脑室旁核c-fos阳性细胞数明显减少,平均目标灰度值明显增高。研究结论如下： 1.急、慢性应激均减少小鼠的开场行为活动,但在慢性应激条件下更为明显。 2.急性应激明显增强小鼠的空间学习记忆能力；慢性应激则明显损害小鼠的空间学习记忆能力。 3.急性应激对小鼠神经元形态结构无明显影响；慢性应激则导致小鼠海马、前脑皮层和下丘脑室旁核神经元发生明显的形态学变化。 4.急性应激可使小鼠海马、前脑皮层及下丘脑室旁核c-fos表达明显上调；慢性应激则使小鼠海马区、前脑皮层及下丘脑室旁核神经元中c-fos表达明显下调。研究结果表明,急性应激导致小鼠自发行为和空间学习记忆能力的变化可能与与血清皮质酮的急剧上升及脑海马、前脑皮层和下丘脑室旁核c-fos的大量表达有关；而慢性应激导致小鼠自发行为抑制和空间学习记忆能力受损亦可能与长期高水平皮质酮,脑海马、前脑皮层和下丘脑室旁核神经元的损害及c-fos表达的明显下调密切相关。
[Abstract]:In this study, the animal models of single factor acute stress (foot shock) and multi factor chronic unpredictable stress animal models (congestion, cold / heat stimulation, white noise, high platform, foot shock, 28 days) were used to study the changes in spontaneous behavior and learning and memory ability of mice and the changes in the expression of c-fos in the brain under acute and chronic stress conditions. The effect and mechanism of different stress conditions on spontaneous behavior and spatial learning and memory ability of mice were investigated. The spontaneous behavior of mice under the new environment was detected by the open field experiment; the ability of learning and memory of mice was tested by Morris water maze; the content of corticosterone in serum of mice was determined by enzyme linked immunoassay, and HE was stained by the enzyme linked immunosorbent assay. The morphological changes of the neurons in the hippocampus, the prefrontal cortex and the paraventricular nucleus of the hypothalamus were observed, and the expression of c-fos in the hippocampus, the prefrontal cortex and the paraventricular nucleus of the hypothalamus was detected by immunohistochemistry.
The results of the study are as follows:
1. after acute stress, compared with the control group, the level of the mice in the stress group traversed the number of lattices, the erect times, the number of fecal particles significantly decreased, the residence time of the central lattice was significantly prolonged, but the number of modification times had no significant changes. After chronic stress, the level of the mice in the stress group passed the number of lattice, erect times, and the times of modification were all clear. The number of stool grains increased significantly.
2. after acute stress, compared with the control group, the escape latency of the search platform in the stress group was obviously shortened, and the stay time in the target quadrant was obviously prolonged in the space search experiment. After the chronic stress, the escape latency of the stress group was obviously prolonged and the space search experiment was compared with the control group. In the target quadrant, the stay time is obviously shortened.
3. acute, chronic stress, compared with the control group, the levels of serum corticosterone in the stress group increased significantly, but the degree of acute stress increased more.
4. after acute stress, compared with the control group, the neuronal morphology and structure of the mice in the stress group did not change obviously. After chronic stress, the number of neurons in the hippocampus, the prefrontal cortex and the paraventricular nucleus of the hypothalamus in the stress group was significantly reduced, and the cells atrophied and showed varying degrees of damage after the stress group.
5. after acute stress, compared with the control group, the number of c-fos positive cells in the hippocampus, the prefrontal cortex and the paraventricular nucleus of the hypothalamus increased significantly in the stress group, and the average target gray value decreased obviously. After chronic stress, the number of c-fos positive cells in the hippocampus, the prefrontal cortex and the paraventricular nucleus of the hypothalamus in the stress group decreased significantly. The gray value of all target is obviously higher.
The conclusions are as follows:
1. acute and chronic stress reduced the opening behavior of mice, but it was more obvious under chronic stress.
2. acute stress significantly enhanced spatial learning and memory ability in mice, while chronic stress significantly impaired spatial learning and memory ability in mice.
3. acute stress had no obvious effect on the morphological structure of neurons in mice, and the chronic stress resulted in obvious morphological changes in the neurons of the hippocampus, the prefrontal cortex and the paraventricular nucleus of the inferior colliculus.
4. acute stress can increase the expression of c-fos in the hippocampus, the prefrontal cortex and the paraventricular nucleus of the hypothalamus, and the expression of c-fos in the neurons of the hippocampus, the prefrontal cortex and the paraventricular nucleus of the inferior colliculus of mice is obviously down regulated by chronic stress.
The results suggest that the changes in spontaneous behavior and spatial learning and memory of mice induced by acute stress may be associated with a sharp rise in serum corticosterone and a large number of expressions of c-fos in the hippocampus, the prefrontal cortex and the paraventricular nucleus of the inferior colliculus, while chronic stress may cause damage to the self release and spatial learning and memory ability of mice. Chronic high levels of corticosterone, brain hippocampus, forebrain cortex and hypothalamic paraventricular nucleus damage were closely related to the down-regulation of c-fos expression.
【学位授予单位】：曲阜师范大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363

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