慢性应激对小鼠空间学习记忆功能及脑内BDNF表达的影响

发布时间：2018-06-07 02:28

本文选题：慢性应激 + 空间学习记忆　；参考：《曲阜师范大学》2009年硕士论文

【摘要】： 许多研究显示慢性应激可损害健康,引发疾病,同时也可影响脑的认知功能,导致学习记忆能力下降。脑源性神经营养因子(BDNF)是神经营养素家族的成员之一,它不仅对神经元的生存、生长、分化有重要的影响,而且还能增强突触联系,影响神经元的可塑性,并且与学习记忆有关。本研究采用多因素慢性(电击足底、拥挤、拥挤+热刺激,15天)应激动物模型,研究了慢性应激对不同月龄小鼠(2月龄和15月龄)空间学习记忆能力的损害作用及其BDNF在海马和前脑皮层的表达变化。旨在探讨慢性应激对不同月龄小鼠空间学习记忆功能的影响及BDNF的作用,从而为指导临床用药提供一种新的措施和思路。本研究以开场行为检测小鼠在新异环境中的自发活动;采用Morris水迷宫测试小鼠空间学习记忆能力;通过HE染色观察小鼠海马和前脑皮层神经细胞形态学的变化;采用免疫组织化学方法检测BDNF在海马和前脑皮层的表达。研究结果如下: 1.与对照组小鼠相比,青年应激组小鼠的爬行格数、直立次数及修饰次数均明显减少,这一变化趋势在老年应激组小鼠更明显,而粪便粒数没有显著性变化。与青年对照组小鼠相比,老年对照组小鼠的修饰次数显著减少。与青年应激组小鼠相比,老年应激组小鼠爬行格数及修饰次数明显减少。 2.应激组小鼠寻找平台的潜伏期较对照组小鼠明显增加,且在空间搜索试验中,在目标象限的停留时间较对照组小鼠明显缩短,这种状态持续到停止应激后一周。分别与青年对照组和应激组小鼠相比,老年对照组和应激组小鼠的空间学习记忆能力略有降低,但是没有统计学意义。 3.应激组小鼠海马神经细胞的排列较对照组小鼠明显疏松,细胞缺失,尼氏体浅染甚至溶解。前脑皮层神经细胞也呈程度不同的损伤现象。与青年应激组小鼠相比,老年应激组小鼠的损伤更加严重。这种变化持续到停止应激后一周。 4.应激组小鼠海马和前脑皮层BDNF表达均明显下调,阳性细胞数明显减少,阳性细胞面积比显著减小。老年应激组小鼠变化尤为明显。分别与青年对照组和应激组小鼠相比,老年对照组和应激组小鼠BDNF的表达显著降低。研究结论如下: 1.老年小鼠对新异环境的反应性和耐受性均下降,慢性应激后表现的更显著,说明衰老是影响机体应激反应性的重要因素之一。 2.慢性应激明显损害小鼠的空间学习记忆能力,老年小鼠的空间学习记忆能力下降更明显。 3.慢性应激导致小鼠海马和前脑皮层神经细胞的形态学变化,老年组小鼠神经细胞形态学改变较青年组小鼠加重。 4.慢性应激可使小鼠海马和前脑皮层BDNF的表达下降,老年组小鼠在海马和前脑皮层BDNF的表达均较青年组小鼠下降明显。本研究发现,慢性应激后即刻及停止应激后一周,小鼠的空间学习记忆功能的损伤与海马和前脑皮层中BDNF表达的变化相一致,提示慢性应激损害小鼠的空间学习记忆功能以及停止应激后的恢复过程中,脑内BDNF对其都发挥了重要的保护作用。
[Abstract]:Many studies have shown that chronic stress can damage health, cause disease, and also affect the cognitive function of the brain, resulting in a decline in learning and memory. BDNF is one of the members of the neurotrophic family, which not only affects the survival, growth, and differentiation of neurons, but also enhances synaptic connections. The plasticity of ringing neurons is related to learning and memory. In this study, the effects of chronic stress on the spatial learning and memory ability of different months of age (2 month old and 15 month old) and the changes in the expression of BDNF in the hippocampus and prefrontal cortex were studied by multiple factors chronic (electric shock, crowding, congestion + heat stimulation, 15 days). The purpose of this study is to explore the effect of chronic stress on the function of spatial learning and memory in mice of different months of age and the role of BDNF, so as to provide a new way to guide clinical medication.
In this study, the spontaneous activity of mice in the new environment was detected by the opening behavior; the Morris water maze was used to test the spatial learning and memory ability of mice; the morphological changes in the hippocampus and prefrontal cortex of mice were observed by HE staining, and the expression of BDNF in the hippocampus and prefrontal cortex was detected by immunohistochemistry.
The results of the study are as follows:
1. compared with the control group, the number of creeping, the erect times and the number of modification of the mice in the young stress group were significantly reduced, and the change trend was more obvious in the elderly stress group, but the number of fecal particles did not change significantly. Compared with the young control group, the number of modification times of the old control group decreased significantly. Compared with mice, the number of crawling lattices and the number of times of modification in the aged stress group decreased significantly.
In the 2. stress group, the incubation period of the finding platform was significantly higher than that of the control group. In the space search test, the stay time in the target quadrant was significantly shorter than the control group. This state lasted to the week after the stop stress. Compared with the young control group and the stress group, the spatial learning of the elderly control group and the stress group was compared with the stress group. The ability of learning and memory decreased slightly, but there was no statistical significance.
The hippocampal neurons in the 3. stress group were obviously looser than those in the control group, the cell loss, the Nissl body light staining and even dissolving. The nerve cells in the prefrontal cortex also showed a different degree of damage. Compared with the young stress group, the injury of the aged stress group was more serious. This change continued until the week after the stress was stopped.
In 4. stress group, the expression of BDNF in hippocampus and prefrontal cortex of mice was obviously decreased, the number of positive cells decreased and the ratio of positive cell area decreased significantly. The changes of mice in the elderly stress group were particularly obvious. Compared with the young control group and the stress group, the expression of BDNF in the elderly control group and the stress group decreased significantly.
The conclusions are as follows:
1. the reactivity and tolerance of the aged mice to the new environment decreased and the chronic stress was more significant, indicating that aging was one of the important factors affecting the stress responsiveness of the body.
2. chronic stress significantly impaired the spatial learning and memory ability of mice, and the spatial learning and memory ability of aged mice decreased more significantly.
3. chronic stress induced morphological changes of neurons in hippocampus and forebrain cortex of mice. The morphological changes of neurons in aged group were more serious than those in young mice.
4. chronic stress can reduce the expression of BDNF in the hippocampus and prefrontal cortex of mice. The expression of BDNF in the hippocampus and prefrontal cortex of the aged mice is significantly lower than that of the young mice.
This study found that the impairment of spatial learning and memory function in mice was consistent with the changes in the expression of BDNF in the hippocampus and prefrontal cortex after the immediate and halt stress after chronic stress. It suggested that the BDNF in the brain played an important role in the damage of the spatial learning and memory function of mice and the recovery process after the stress was stopped. Protection.
【学位授予单位】：曲阜师范大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R363

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