慢性轻度不可预知性应激对不同月龄大鼠不同脑区BDNF表达的影响
发布时间：2019-01-08 10:24
【摘要】： 应激(Stress)是指面临内外环境剧变时，机体所做出的包括精神、神经、内分泌、免疫等反应的综合性应答状态。应激时，除下丘脑-垂体-肾上腺皮质(HPA)轴和蓝斑-交感神经-肾上腺髓质系统(LC-AN-AMS)过度活动外，下丘脑-垂体-甲状腺(HPT)轴、下丘脑-垂体-性腺(HPG)轴等也参与应激反应过程。 慢性应激过程中，持续的HPA轴功能亢进和高浓度的糖皮质激素(GCs)是造成机体损伤的病理学基础。在中枢神经系统中，海马、前额叶皮层及纹状体等部位是与认知、情绪及行为功能密切相关的重要脑区，由于富含糖皮质激素受体(GR)而成为高浓度GCs攻击的主要靶区。慢性应激会导致海马锥体细胞的变性和坏死、前额叶皮层体积变小和神经元坏死以及纹状体单胺类神经递质的含量下降。在针对与慢性应激密切相关的疾病如抑郁症的研究中发现，抑郁症患者海马、前额叶皮层、腹侧纹状体的体积减小。 有研究显示，生理和情绪应激与脑源性神经营养因子(BDNF)的表达关系密切。BDNF属于神经营养素(NTs)家族，主要在中枢神经系统内表达，分布在海马、杏仁核、纹状体和皮层等部位，不仅能促进神经元生存、延缓神经元的变性和自然死亡，对胆碱能神经元、多巴胺能神经元、运动神经元、γ-氨基丁酸(GABA)能神经元有营养作用，而且作为应激保护因子在应激过程中也发挥重要作用。研究证明，慢性应激可导致大鼠海马CA3区以及前额叶皮层BDNF的表达明显降低。机体对应激的反应性和耐受性与年龄有密切关系。如有研究发现，啮齿类衰老动物血中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、GCs的浓度显著升高，对慢性应激反应超敏。 本研究采用慢性轻度不可预知性应激(CUMS)建立应激动物模型，对不同月龄(2月龄和15月龄共72只)Wistar大鼠的行为学及海马CA3区、齿状回、前额叶皮层及纹状体中BDNF的表达进行研究，比较慢性应激对不同衰老程度大鼠行为学及关键脑区BDNF表达的影响。实验结果如下： 1．与对照组相比，两月龄应激大鼠的中央格停留时间延长，跨格数、直立次数及清洁次数均明显减少，这一变化趋势在老年应激组更明显。与青年应激组相比，老年应激组大鼠中央格停留时间延长，跨格数及直立次数减少。 2．应激组大鼠的糖水消耗量和糖水偏爱百分比都显著低于对照组，而纯水消耗量则显著高于对照组，总液体消耗在整个应激过程中呈下降趋势并持续到应激结束后一周，但差异不具有统计学意义。和青年应激组相比，老年应激组的糖水消耗量和糖水偏爱百分比降低。 3．应激组大鼠海马CA3区及齿状回细胞的排列明显较对照组稀疏，细胞间隙加大，细胞淡染、肿胀、萎缩变性明显。前额叶皮层及纹状体神经细胞也呈程度不同的细胞损伤现象。与青年应激组相比，老年应激组的损伤更加严重。这种变化持续到应激后一周。 4．应激组海马、纹状体及皮层BDNF表达均明显下调，阳性细胞数量减少，着色变浅，BDNF免疫反应阳性产物的光密度值明显低于对照组，平均灰度值增加。老年应激组变化尤为明显。应激后一周，青年应激组BDNF的表达有一定程度的升高，但仍显著低于对照组。 研究结论如下： 1．慢性轻度不可预知性应激对不同月龄大鼠的行为学影响不同，老年大鼠的行为学改变较青年大鼠显著。提示伴随机体衰老，大鼠对应激的反应性和耐受性均下降，说明衰老是影响机体应激反应性的重要因素之一。 2．慢性轻度不可预知性应激可降低大鼠的糖水消耗量和糖水偏爱百分比，，老年大鼠较青年大鼠下降明显。提示慢性应激可造成动物的快感缺失，老年动物的快感缺失更明显。 3．慢性轻度不可预知性应激可造成大鼠海马CA3区和齿状回、纹状体及前额叶皮层神经细胞的形态学变化，主要表现为细胞数量减少，排列紊乱，细胞变性萎缩甚至死亡。老年大鼠神经细胞形态学改变较青年大鼠严重。 4．慢性轻度不可预知性应激可造成大鼠海马CA3区和齿状回、前额叶皮层、纹状体BDNF表达下降，以海马CA3区和齿状回下降最为显著。老年大鼠在各脑区的表达均较青年大鼠下降明显。
[Abstract]:Stress (stress) refers to the state of comprehensive response, including spirit, nerve, endocrine, immunity, and so on, which is made by the body when the internal and external environment plays a very important role. In stress, the hypothalamic-pituitary-thyroid (HPT) axis, the hypothalamic-pituitary-gonad (HPG) axis, and the like also participate in the stress response process in addition to the hyperactivity of the hypothalamic-pituitary-adrenal cortex (HPA) axis and the blue-spot-sympathetic-adrenal medulla system (LC-AN-AMS). In the course of chronic stress, persistent HPA axis hyperfunction and high concentration of glucocorticoid (GCs) are the cause of the machine The pathological basis of body injury. In the central nervous system, the cortex and the striatum of the hippocampus, the prefrontal cortex and the striatum are important brain regions which are closely related to the cognition, the mood and the behavior function, because the glucocorticoid receptor (GR) is rich in the high concentration G. The main target area of the Cs attack. The chronic stress can lead to degeneration and necrosis of the pyramidal cells in the hippocampus, the volume of the prefrontal cortex and the neuronal necrosis, and the monoamines in the striatum. The content of neurotransmitters is reduced. In the study of diseases associated with chronic stress, such as depression, the hippocampus, the prefrontal cortex, the abdomen, The volume of the striatum of the lateral striatum is reduced. It is shown that the physiological and emotional stress and the source of the brain The expression of BDNF is closely related to the expression of the neurotrophic factor (BDNF). The BDNF belongs to the neurotrophin (NTs) family, which is mainly expressed in the central nervous system, and is distributed in the hippocampus, the amygdala, the striatum and the cortex, which not only can promote the survival of the neurons, and delay the degeneration and the self-adaptation of the neurons. in that case of death, the cholinergic neuron, the dopaminergic neuron, the motor neuron, the p-aminobutyric acid (GABA), The stress protection factor also plays an important role in the stress process. The study shows that the chronic stress can lead to the CA3 in the rat's hippocampus. The expression of BDNF in the cortex and prefrontal cortex is significantly reduced. The reactivity and tolerability of stress are closely related to age, as has been found in the study that the corticotropin-releasing hormone (CRH), the corticotropin (ACTH), G, In this study, a stress animal model of chronic mild non-predictable stress (CUMS) was used to establish a stress animal model, and the behavior and hippocampus of Wistar rats at different ages (2 months and 15 months) were studied in this study. The expression of BDNF in the area of A3, dentate gyrus, prefrontal cortex and striatum was studied. sexual stress The results of the experimental results are as follows: 1. In comparison with the control group, the central cell of the two-month-old stress rats the time is prolonged, the number of cross cells, the number of upright times and the number of cleaning are obviously reduced, and the variation trend is higher in the old stress group Obvious. Compared with the youth stress group, the residence time of the central cell of the old stress group was prolonged, the number of cross-cells and the number of upright times decreased. The sugar and water consumption and the preference percentage of the sugar water in the stress group were significantly lower than that of the control group, while the consumption of pure water The total fluid consumption was significantly higher in the whole stress process than in the control group and continued to be A week after the end of the shock, the difference was not statistically significant. The sugar water consumption and the percentage of sugar water preference decreased in the old stress group as compared to the youth stress group. 3. CA3 and dentate gyrus of hippocampus in rats with stress group The arrangement is obviously less than the control group, the cell gap is increased, and the cell is light-dyed. Swollen, atrophied. Forehead. The damage of the cortex and the striatum of the striatum was also different, and the damage of the old stress group was more severe than that of the young stress group. The change lasted a week after the stress. Hippocampus, striatum and cortex B of shock group The expression of DNF was down-regulated, the number of positive cells was reduced, the staining was light, and the expression of BDNF was positive. the optical density value is obvious The average gray-scale value of the group was lower than that of the control group. The change of the old stress group was especially obvious. The expression of BDNF in the young stress group was a certain week after the stress. The results of the study were as follows: 1. Chronic mild The effect of non-predictable stress on the behavior of rats with different months of age was different, and the behavior of the old rats was more significant than that of the young rats. The aging of the body and the response and tolerance of the rat to the stress are both decreased, indicating that the aging is the effect of the body. One of the most important factors of stress response. 2. Chronic mild non-predictable stress can reduce the sugar water consumption and the preference percentage of the sugar water in the rats, and the aged rats are obviously lower than the young rats. It is suggested that the chronic stress can As a result of the loss of the animal's pleasure, the sensual pleasure of the old animal is more clear The morphological changes of the neurons in the CA3 region and the dentate gyrus, the striatum and the prefrontal cortex of the rat hippocampal CA3 region and the prefrontal cortex of the rat can be caused by the chronic mild unpredictable stress. The number of cells is reduced, the arrangement disorder, the degeneration of the cells, and even death
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R395
本文编号：2404477
[Abstract]:Stress (stress) refers to the state of comprehensive response, including spirit, nerve, endocrine, immunity, and so on, which is made by the body when the internal and external environment plays a very important role. In stress, the hypothalamic-pituitary-thyroid (HPT) axis, the hypothalamic-pituitary-gonad (HPG) axis, and the like also participate in the stress response process in addition to the hyperactivity of the hypothalamic-pituitary-adrenal cortex (HPA) axis and the blue-spot-sympathetic-adrenal medulla system (LC-AN-AMS). In the course of chronic stress, persistent HPA axis hyperfunction and high concentration of glucocorticoid (GCs) are the cause of the machine The pathological basis of body injury. In the central nervous system, the cortex and the striatum of the hippocampus, the prefrontal cortex and the striatum are important brain regions which are closely related to the cognition, the mood and the behavior function, because the glucocorticoid receptor (GR) is rich in the high concentration G. The main target area of the Cs attack. The chronic stress can lead to degeneration and necrosis of the pyramidal cells in the hippocampus, the volume of the prefrontal cortex and the neuronal necrosis, and the monoamines in the striatum. The content of neurotransmitters is reduced. In the study of diseases associated with chronic stress, such as depression, the hippocampus, the prefrontal cortex, the abdomen, The volume of the striatum of the lateral striatum is reduced. It is shown that the physiological and emotional stress and the source of the brain The expression of BDNF is closely related to the expression of the neurotrophic factor (BDNF). The BDNF belongs to the neurotrophin (NTs) family, which is mainly expressed in the central nervous system, and is distributed in the hippocampus, the amygdala, the striatum and the cortex, which not only can promote the survival of the neurons, and delay the degeneration and the self-adaptation of the neurons. in that case of death, the cholinergic neuron, the dopaminergic neuron, the motor neuron, the p-aminobutyric acid (GABA), The stress protection factor also plays an important role in the stress process. The study shows that the chronic stress can lead to the CA3 in the rat's hippocampus. The expression of BDNF in the cortex and prefrontal cortex is significantly reduced. The reactivity and tolerability of stress are closely related to age, as has been found in the study that the corticotropin-releasing hormone (CRH), the corticotropin (ACTH), G, In this study, a stress animal model of chronic mild non-predictable stress (CUMS) was used to establish a stress animal model, and the behavior and hippocampus of Wistar rats at different ages (2 months and 15 months) were studied in this study. The expression of BDNF in the area of A3, dentate gyrus, prefrontal cortex and striatum was studied. sexual stress The results of the experimental results are as follows: 1. In comparison with the control group, the central cell of the two-month-old stress rats the time is prolonged, the number of cross cells, the number of upright times and the number of cleaning are obviously reduced, and the variation trend is higher in the old stress group Obvious. Compared with the youth stress group, the residence time of the central cell of the old stress group was prolonged, the number of cross-cells and the number of upright times decreased. The sugar and water consumption and the preference percentage of the sugar water in the stress group were significantly lower than that of the control group, while the consumption of pure water The total fluid consumption was significantly higher in the whole stress process than in the control group and continued to be A week after the end of the shock, the difference was not statistically significant. The sugar water consumption and the percentage of sugar water preference decreased in the old stress group as compared to the youth stress group. 3. CA3 and dentate gyrus of hippocampus in rats with stress group The arrangement is obviously less than the control group, the cell gap is increased, and the cell is light-dyed. Swollen, atrophied. Forehead. The damage of the cortex and the striatum of the striatum was also different, and the damage of the old stress group was more severe than that of the young stress group. The change lasted a week after the stress. Hippocampus, striatum and cortex B of shock group The expression of DNF was down-regulated, the number of positive cells was reduced, the staining was light, and the expression of BDNF was positive. the optical density value is obvious The average gray-scale value of the group was lower than that of the control group. The change of the old stress group was especially obvious. The expression of BDNF in the young stress group was a certain week after the stress. The results of the study were as follows: 1. Chronic mild The effect of non-predictable stress on the behavior of rats with different months of age was different, and the behavior of the old rats was more significant than that of the young rats. The aging of the body and the response and tolerance of the rat to the stress are both decreased, indicating that the aging is the effect of the body. One of the most important factors of stress response. 2. Chronic mild non-predictable stress can reduce the sugar water consumption and the preference percentage of the sugar water in the rats, and the aged rats are obviously lower than the young rats. It is suggested that the chronic stress can As a result of the loss of the animal's pleasure, the sensual pleasure of the old animal is more clear The morphological changes of the neurons in the CA3 region and the dentate gyrus, the striatum and the prefrontal cortex of the rat hippocampal CA3 region and the prefrontal cortex of the rat can be caused by the chronic mild unpredictable stress. The number of cells is reduced, the arrangement disorder, the degeneration of the cells, and even death
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R395
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