慢性輕度不可預(yù)知性應(yīng)激對不同月齡大鼠不同腦區(qū)BDNF表達的影響
發(fā)布時間：2019-01-08 10:24
【摘要】： 應(yīng)激(Stress)是指面臨內(nèi)外環(huán)境劇變時，機體所做出的包括精神、神經(jīng)、內(nèi)分泌、免疫等反應(yīng)的綜合性應(yīng)答狀態(tài)。應(yīng)激時，除下丘腦-垂體-腎上腺皮質(zhì)(HPA)軸和藍斑-交感神經(jīng)-腎上腺髓質(zhì)系統(tǒng)(LC-AN-AMS)過度活動外，下丘腦-垂體-甲狀腺(HPT)軸、下丘腦-垂體-性腺(HPG)軸等也參與應(yīng)激反應(yīng)過程。 慢性應(yīng)激過程中，持續(xù)的HPA軸功能亢進和高濃度的糖皮質(zhì)激素(GCs)是造成機體損傷的病理學基礎(chǔ)。在中樞神經(jīng)系統(tǒng)中，海馬、前額葉皮層及紋狀體等部位是與認知、情緒及行為功能密切相關(guān)的重要腦區(qū)，由于富含糖皮質(zhì)激素受體(GR)而成為高濃度GCs攻擊的主要靶區(qū)。慢性應(yīng)激會導(dǎo)致海馬錐體細胞的變性和壞死、前額葉皮層體積變小和神經(jīng)元壞死以及紋狀體單胺類神經(jīng)遞質(zhì)的含量下降。在針對與慢性應(yīng)激密切相關(guān)的疾病如抑郁癥的研究中發(fā)現(xiàn)，抑郁癥患者海馬、前額葉皮層、腹側(cè)紋狀體的體積減小。 有研究顯示，生理和情緒應(yīng)激與腦源性神經(jīng)營養(yǎng)因子(BDNF)的表達關(guān)系密切。BDNF屬于神經(jīng)營養(yǎng)素(NTs)家族，主要在中樞神經(jīng)系統(tǒng)內(nèi)表達，分布在海馬、杏仁核、紋狀體和皮層等部位，不僅能促進神經(jīng)元生存、延緩神經(jīng)元的變性和自然死亡，對膽堿能神經(jīng)元、多巴胺能神經(jīng)元、運動神經(jīng)元、γ-氨基丁酸(GABA)能神經(jīng)元有營養(yǎng)作用，而且作為應(yīng)激保護因子在應(yīng)激過程中也發(fā)揮重要作用。研究證明，慢性應(yīng)激可導(dǎo)致大鼠海馬CA3區(qū)以及前額葉皮層BDNF的表達明顯降低。機體對應(yīng)激的反應(yīng)性和耐受性與年齡有密切關(guān)系。如有研究發(fā)現(xiàn)，嚙齒類衰老動物血中促腎上腺皮質(zhì)激素釋放激素(CRH)、促腎上腺皮質(zhì)激素(ACTH)、GCs的濃度顯著升高，對慢性應(yīng)激反應(yīng)超敏。 本研究采用慢性輕度不可預(yù)知性應(yīng)激(CUMS)建立應(yīng)激動物模型，對不同月齡(2月齡和15月齡共72只)Wistar大鼠的行為學及海馬CA3區(qū)、齒狀回、前額葉皮層及紋狀體中BDNF的表達進行研究，比較慢性應(yīng)激對不同衰老程度大鼠行為學及關(guān)鍵腦區(qū)BDNF表達的影響。實驗結(jié)果如下： 1．與對照組相比，兩月齡應(yīng)激大鼠的中央格停留時間延長，跨格數(shù)、直立次數(shù)及清潔次數(shù)均明顯減少，這一變化趨勢在老年應(yīng)激組更明顯。與青年應(yīng)激組相比，老年應(yīng)激組大鼠中央格停留時間延長，跨格數(shù)及直立次數(shù)減少。 2．應(yīng)激組大鼠的糖水消耗量和糖水偏愛百分比都顯著低于對照組，而純水消耗量則顯著高于對照組，總液體消耗在整個應(yīng)激過程中呈下降趨勢并持續(xù)到應(yīng)激結(jié)束后一周，但差異不具有統(tǒng)計學意義。和青年應(yīng)激組相比，老年應(yīng)激組的糖水消耗量和糖水偏愛百分比降低。 3．應(yīng)激組大鼠海馬CA3區(qū)及齒狀回細胞的排列明顯較對照組稀疏，細胞間隙加大，細胞淡染、腫脹、萎縮變性明顯。前額葉皮層及紋狀體神經(jīng)細胞也呈程度不同的細胞損傷現(xiàn)象。與青年應(yīng)激組相比，老年應(yīng)激組的損傷更加嚴重。這種變化持續(xù)到應(yīng)激后一周。 4．應(yīng)激組海馬、紋狀體及皮層BDNF表達均明顯下調(diào)，陽性細胞數(shù)量減少，著色變淺，BDNF免疫反應(yīng)陽性產(chǎn)物的光密度值明顯低于對照組，平均灰度值增加。老年應(yīng)激組變化尤為明顯。應(yīng)激后一周，青年應(yīng)激組BDNF的表達有一定程度的升高，但仍顯著低于對照組。 研究結(jié)論如下： 1．慢性輕度不可預(yù)知性應(yīng)激對不同月齡大鼠的行為學影響不同，老年大鼠的行為學改變較青年大鼠顯著。提示伴隨機體衰老，大鼠對應(yīng)激的反應(yīng)性和耐受性均下降，說明衰老是影響機體應(yīng)激反應(yīng)性的重要因素之一。 2．慢性輕度不可預(yù)知性應(yīng)激可降低大鼠的糖水消耗量和糖水偏愛百分比，，老年大鼠較青年大鼠下降明顯。提示慢性應(yīng)激可造成動物的快感缺失，老年動物的快感缺失更明顯。 3．慢性輕度不可預(yù)知性應(yīng)激可造成大鼠海馬CA3區(qū)和齒狀回、紋狀體及前額葉皮層神經(jīng)細胞的形態(tài)學變化，主要表現(xiàn)為細胞數(shù)量減少，排列紊亂，細胞變性萎縮甚至死亡。老年大鼠神經(jīng)細胞形態(tài)學改變較青年大鼠嚴重。 4．慢性輕度不可預(yù)知性應(yīng)激可造成大鼠海馬CA3區(qū)和齒狀回、前額葉皮層、紋狀體BDNF表達下降，以海馬CA3區(qū)和齒狀回下降最為顯著。老年大鼠在各腦區(qū)的表達均較青年大鼠下降明顯。
[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
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R395
本文編號：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
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R395
【參考文獻】
相關(guān)期刊論文 前3條
1 賴紅;曾亮;趙海花;高杰;王鐵民;呂永利;;老齡大鼠海馬結(jié)構(gòu)腦源性神經(jīng)營養(yǎng)因子表達的改變[J];解剖學雜志;2005年06期
2 司銀楚,朱培純;去腦皮層血管對大鼠前腦大細胞基底核AChE、ChAT、BDNF、trkB及其mRNA表達的影響[J];神經(jīng)解剖學雜志;2001年02期
3 許晶,李曉秋;慢性應(yīng)激抑郁模型的建立及其評價[J];中國行為醫(yī)學科學;2003年01期
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