恐惧声音心理应激对不同阶段制小鼠学习记忆的影响机

发布时间：2018-01-01 11:06

本文关键词：恐惧声音心理应激对不同阶段制小鼠学习记忆的影响机　出处：《陕西师范大学》2008年硕士论文　论文类型：学位论文

【摘要】： 许多文献报道,心理应激能够损伤动物空间学习和记忆能力。而且随着社会竞争、工作压力以及家庭变异等社会应激源的逐步增加,心理因素相关疾病的发生率具有迅速增长的趋势。因此,心理应激与学习记忆的关系以及对学习记忆能力的影响的研究也就成为生命科学领域的热点。目前,国内关于研究心理应激与学习记忆的模型很多,如力竭游泳、束缚、热应激以及电击等,它们均存在躯体应激利心理应激两种过程,难以评估单纯心理应激的对学习记忆的影响效应;国外,对心理应激与学习记忆关系的研究也仅是处于慢性应激的阶段。本实验通过建立的恐惧声音心理应激模型,将实验动物分为对照组、孕期组、幼年组以及青年组。观察不同阶段鼠龄小鼠的行为,畸形情况,并定期称量各组小鼠的体重;采用Morris水迷宫检测不同时期不同性别小鼠的空间学习记忆水平,以探测妊娠期、幼年期以及青年期小鼠接受应激刺激后对学习记忆能力的影响;通过荧光免疫组织化学方法观察妊娠期、幼年期以及青年期接受刺激后各组小鼠海马结构中N-甲基-D-天冬氨酸受体1(N-methyl-D-aspartic acidreceptor1,NMDAR1)的表达情况,探讨应激影响对各组不同性别小鼠学习记忆能力的可能机制;高频刺激(High frequency stimulation,HFS)被广泛用来研究海马CA1区长时程增强(Long-term potentiation,LTP)的诱导和维持的动力学特点,Schaffer侧枝-CA1通路的LTP又是研究突触可塑性的常用模型,本研究还通过高频刺激,观察孕期和幼年期小鼠的海马处Schaffer侧枝-CA1区LTP的诱发幅度。行为观察及体重称量结果显示,和对照组相比,恐惧声音心理应激对不同时期雌性小鼠的行为有明显的影响,表现为两耳竖立、身体卷曲,将头埋藏于刨花中;有打洞逃离的行为,不易捕捉,对人的恐惧水平提高,挣扎的程度增加;大小便频繁、扎堆;恐惧声音心理应激可抑制不同时期小鼠的体重的增加量,尤其是幼年声音组表现尤为明显,雄鼠的情况正好相反。另外,对小鼠出生率及成活率基本没有影响。 Morris水迷宫实验结果表明:空间搜索策略一恐惧声音应激后,较对照组相比,孕期和幼年声音组小鼠基本上没有形成参考认知能力,青年声音组基本上形成了参考认知能力,但较对照组差;学习能力一恐惧声音心理应激能够促进雌鼠的学习能力,但抑制雄鼠的学习能力;记忆能力—Morris水迷宫实验结果表明,恐惧声音心理应激对孕鼠的仔鼠记忆有促进作用,但是对幼年和青年时期的小鼠的记忆能力有抑制作用;另外,恐惧声音对不同性别的小鼠的影响也不同,对于雌鼠,恐惧声音心理应激抑制幼年期和青年期的雌鼠的记忆能力,促进孕鼠的雌性后代的记忆;对于雄鼠,恐惧声音刺激对幼年期和青年期的雄鼠的空间记忆能力有一定的促进作用,对孕鼠的雄性后代有极大的抑制作用。荧光免疫组化结果表明,恐惧声音心理应激促进了NMDAR1亚单位在雌鼠海马CA1区和CA3区的表达,抑制了其在雌鼠海马齿状回的表达;恐惧声音心理应激抑制NMDAR1亚单位在雄鼠海马CA1区、CA3区以及齿状回的表达。电生理实验结果表明,恐惧声音心理应激对海马CA1区的LTP的形成和诱发有明显的促进作用。以上结果表明,本实验成功建立了恐惧声音心理应激模型。恐惧声音应激对不同时期、不同性别小鼠的行为、体重及学习记忆能力均有不同影响。其影响的分子机制在于改变小鼠海马CA1和CA3区NMDAR1亚单位的表达,并促进海马CA1区的LTP形成和诱发。
[Abstract]:Many reports in the literature, psychological stress can damage animal spatial learning and memory ability. With the social competition, work stress and family variation and other social stressors gradually increase the diseases related to psychological factors have been growing rapidly. Therefore, research on psychological relationship between learning and memory and shock effect on the ability of learning and memory has become a hotspot in the field of life science. At present, many domestic research on psychological stress and learning and memory model, such as swimming, restraint, heat stress and electric shocks, are the psychological stress physical stresses and two kinds of process, it is difficult to assess the effect on learning and memory of psychological stress; abroad study on the relationship between psychological stress and learning and memory is only at the level of the chronic stress.
Through the experiments of terrified sound stress model, the experimental animal were divided into control group, pregnancy group, infant group and youth group. Rats were observed at different stages of mouse behavior, abnormal, and regularly weighed the mice body weight; using the Morris water maze test in different periods of different sex mice spatial learning and memory level, to detect pregnancy, infancy and young mice received stress stimulation effect on the ability of learning and memory; by fluorescence immunohistochemistry method to observe the pregnancy, infancy and adolescence when stimulated mice in hippocampus of N- methyl -D- aspartate receptor 1 (N-methyl-D-aspartic, acidreceptor1, NMDAR1) expression. To explore the possible mechanism of stress effects on learning and memory ability of each group of different sex mice; high frequency stimulation (High frequency, stimulation, HFS) is widely used to study Hippocampal CA1 long-term potentiation (Long-term, potentiation, LTP) in the induction and maintenance of the dynamic characteristics of Schaffer, LTP and -CA1 pathway collateral is a common model for the study of synaptic plasticity, through the high-frequency stimulation evoked amplitude observed during pregnancy and infancy mice hippocampus -CA1 area LTP Schaffer collateral.
Behavior observation and weighing results show that compared with the control group, there is obvious influence behavior of terrified sound stress in different periods of female mice, showed two erect ears, body curled, head buried in a hole in the wood; escape behavior, is not easy to catch, the fear level, struggle the degree of increase; the toilet frequently get together; terrified sound stress can inhibit the weight of mice in different periods increase, especially the youth voice group is obvious in male rats, the opposite is true. In addition, there were no influence on the birthrate and survival rate.
Morris water maze test results show that the space search strategies of terrified sound stress, compared with the control group, the pregnancy and juvenile mice basically did not form a sound reference to cognitive ability, youth voice group basically formed a reference to cognitive ability, but worse than that of control group; psychological stress can promote the learning ability of a sound of fear of female rats learning ability, but the inhibition of male rats, learning ability and memory ability; the experimental results showed that the Morris water maze, rats memory terrified sound stress of pregnant rats was promoted, but has inhibitory effect on youth and youth in the small memory capacity; in addition, affect the sound of fear of different sex mice also different, for female rats, terrified sound stress inhibition of childhood and adolescent female rats memory ability, promote the female offspring of pregnant rats memory; for males, terrified sound stimulation on the young The spatial memory ability of male rats in the year and adolescence has a certain promotion effect, which has a great inhibitory effect on the male offspring of pregnant rats.
Fluorescence immunohistochemistry results showed that the terrified sound stress promoted the expression of NMDAR1 subunit in the hippocampus CA1 area and CA3 area of female rats, inhibit its expression in the dentate gyrus of female rats; terrified sound stress inhibition of NMDAR1 subunit in hippocampus CA1 area of male rats, CA3 region and dentate gyrus of expression.
The results of electrophysiological experiments showed that the psychological stress of fear sounds significantly promoted the formation and induction of LTP in the hippocampal CA1 region.
The above results show that the experiment successfully established the model of terrified sound stress. In different periods of terrified sound stress, mice of different sex behavior, the influence of different weight and the ability of learning and memory. The molecular mechanism of the effect is that the expression change of mice hippocampal CA1 and CA3 regions of NMDAR1 subunit, and promote the formation of LTP in hippocampal CA1 region and induced.

【学位授予单位】：陕西师范大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R395

【引证文献】