規(guī)律運動影響AD模型小鼠腦內單羧酸轉運蛋白表達并改善認知功能
發(fā)布時間：2018-07-25 17:00
【摘要】：阿爾茨海默病(Alzheimer's disease,AD)是一種常見的、呈進行性發(fā)展的、可致死性的中樞神經系統(tǒng)退行性疾病,其病理改變?yōu)?神經元纖維纏結(neurofibrillary tangle,NTF)、老年斑形成(senile plaque,SP)以及神經元變性丟失,臨床上患者常出現(xiàn)進行性認知障礙、記憶減退以及人格改變,并最終發(fā)展為癡呆,一旦罹患此病給個人及家庭都帶來了沉重的負擔。因其高發(fā)病率及致死率的特點,并且其發(fā)病機制尚不清楚,所以是廣大學者積極探討和研究的重點。以往對阿爾茨海默病的研究主要集中在對腦內Aβ蛋白和Tao蛋白的表達上,并且取得了很大的進展。眾所周知,中樞神經系統(tǒng)各項生理活動的維持,需要高能量供給,然而當各種原因引起能量代謝出現(xiàn)障礙時,則可影響神經突觸信息的正常傳遞,引起神經元變性丟失等一系列病理變化,導致機體出現(xiàn)相應的癥狀及改變。近幾年來,許多學者從中樞神經系統(tǒng)能量代謝的角度來深入探討AD的發(fā)病機制及病變過程。大量的實驗數據已經證實了:乳酸可以作為神經元的能量來源為神經系統(tǒng)提供能量,尤其是當神經元和神經膠質細胞不能得到足夠的葡萄糖作為能源物質的時候,乳酸、丙酮酸、酮體等單羧酸類物質則發(fā)揮著舉足輕重的作用。單羧酸類物質跨膜需要載體—單羧酸轉運蛋白(monocarboxylate transporter,MCTs)目前,已經證實了在哺乳動物腦內有MCT1、MCT2、MCT4三種亞型,其中MCT1、MCT4主要位于星形膠質細胞,而MCT2則高表達于神經元,三者協(xié)同將乳酸、丙酮酸、酮體等單羧酸類物質在膠質細胞和神經元之間進行轉運,介導腦內能量代謝,使大腦處于高能量代謝狀態(tài)以此來維持各項生理活動。基于此我們此次試驗通過對不同月齡段的AD模型小鼠進行長時間的規(guī)律有氧運動來進一步闡述MCTs與AD模型小鼠學習、記憶改變的影響及變化。目的探討規(guī)律有氧運動對AD模型小鼠腦內MCT1、MCT2、MCT4表達量的改變以及對其學習、記憶能力的影響。從能量代謝的角度將運動與AD的發(fā)生、發(fā)展聯(lián)系起來,為以后探討AD的發(fā)病機制以及臨床預防、延緩發(fā)病提供理論依據及實驗數據。方法實驗組選擇2、6、10月齡的AD模型小鼠(APP/PS1雙轉基因)和WT野生型小鼠(C57BL/6J),給予8周的游泳訓練至4、8、12月齡。同時選擇未訓練的4、8、12月齡AD模型小鼠和WT野生型小鼠做為對照組。首先采用morris水迷宮對其進行行為學檢測(隱蔽平臺實驗和空間探索實驗),采用western blot檢測腦組織勻漿中MCT1、MCT2、MCT4蛋白表達水平,采用免疫組織化學觀察其大腦皮層和海馬區(qū)MCT1、MCT2、MCT4表達情況。結果(1)morris水迷宮結果顯示:在隱蔽平臺實驗中,經過8周游泳訓練后的小鼠在前兩天內較未訓練組相比平均逃避潛伏期和逃避路程明顯降低,差異具有統(tǒng)計學意義(P0.05),后三天的結果訓練組也較未訓練組低。在空間探索實驗中,訓練組小鼠60s內在目標象限停留的時間明顯高于未訓練組小鼠(P0.05).(2)蛋白表達水平:(我們采用western blot對8月齡的小鼠進行腦組織勻漿蛋白檢測)結果提示:游泳訓練后的AD模型小鼠和WT小鼠較未訓練的表達量顯著增加(P0.05)。(3)免疫組織化學染色:實驗組中MCT1、MCT4在大腦皮層及海馬區(qū)的表達較對照組升高(P0.05)。而MCT2表達水平訓練前后沒有較大的差別。結論長期的規(guī)律有氧運動增加了APP/PS1小鼠腦內MCTs表達量,改善了中樞神經系統(tǒng)能量代謝情況,提高了學習、記憶能力。
[Abstract]:Alzheimer's disease (AD) is a common, progressive, degenerative, degenerative central nervous system degenerative disease, and its pathological changes are: neurofibrillary tangles (neurofibrillary tangle, NTF), senile plaque formation (senile plaque, SP), and neuron degeneration, and clinical patients often have progressive recognition. Cognitive impairment, memory impairment, and personality change, and eventually developing dementia, once the disease has brought a heavy burden on individuals and families. Because of their high incidence and mortality, and their pathogenesis is not yet clear, it is the focus of research and research by many scholars. It is focused on the expression of A beta protein and Tao protein in the brain and has made great progress. It is well known that the maintenance of various physiological activities of the central nervous system requires high energy supply. However, when various reasons cause the disturbance of energy metabolism, it can affect the normal transmission of synapse information and cause degeneration and loss of neurons. A series of pathological changes, resulting in corresponding symptoms and changes in the body. In recent years, many scholars have explored the pathogenesis and pathological process of AD from the angle of the energy metabolism of the central nervous system. A large number of experimental data have proved that lactic acid can provide energy for the nervous system as a source of energy for neurons, especially as a God. Single carboxylic acids, such as lactic acid, pyruvic acid and ketone body, are playing an important role in the absence of sufficient glucose from the cells and glia cells. The single carboxylic acid transmembrane carrier, monocarboxylate transporter (MCTs), has been proved to be in mammalian brain. There are three subtypes of MCT1, MCT2, and MCT4, of which MCT1, MCT4 is mainly located in astrocytes, and MCT2 is highly expressed in neurons. The three parties coordinate the transport of lactate, pyruvic acid, ketone body and other mono carboxylic substances between glia cells and neurons, mediate the energy metabolism in the brain, and keep the brain in high energy metabolic state in order to maintain the various kinds of energy. Physiological activities. Based on this, we further elaborated the effects and changes of memory changes in the learning of MCTs and AD model mice through a long regular aerobic exercise on AD model mice of different months of age. Objective to explore the changes in the expression of MCT1, MCT2, MCT4 in the brain of AD model mice and to study the changes in the expression of MCT1, MCT2 and MCT4 in the brain of AD model mice. The influence of memory ability. From the point of view of energy metabolism, exercise relates to the development of AD, and provides theoretical basis and experimental data for the pathogenesis of AD and clinical prevention and delay of disease. Methods the experimental group selected the AD model mice of 2,6,10 month old (APP/PS1 double transgenic) and WT wild type mice (C57BL/6J) for 8 weeks. The swimming training was 4,8,12 month old. At the same time, the untrained 4,8,12 month old AD model mice and the WT wild type mice were selected as the control group. First, the Morris water maze was used to detect the behavior (hidden platform and space exploration), and the Western blot was used to detect the expression of MCT1, MCT2, MCT4 protein in the homogenization of brain tissue. The expression of MCT1, MCT2, MCT4 in the cerebral cortex and hippocampal region was observed by immunohistochemistry. Results (1) the results of Morris water maze showed that in the hidden platform experiment, the average escape latency and the escape route of mice after 8 weeks of swimming training were significantly lower than those in the untrained group in the first two days, and the difference was statistically significant (P0.05), and three later. In the space exploration experiment, the time of the 60s internal target quadrant in the training group was significantly higher than that in the untrained mice (P0.05). (2) the protein expression level: (we used Western blot to detect the protein in the brain tissue in 8 month old of the mice). The results showed that the AD model after swimming training was small. The expression of untrained mice and WT mice increased significantly (P0.05). (3) immunohistochemical staining: the expression of MCT1 and MCT4 in the cerebral cortex and hippocampus of the experimental group was higher than that in the control group (P0.05). But there was no significant difference between the MCT2 expression level and the MCT2 expression level. Conclusion the long-term regular aerobic exercise increased the expression of MCTs in the brain of APP/PS1 mice. It improves the energy metabolism of central nervous system and improves learning and memory ability.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.16;R-332
本文編號：2144462
[Abstract]:Alzheimer's disease (AD) is a common, progressive, degenerative, degenerative central nervous system degenerative disease, and its pathological changes are: neurofibrillary tangles (neurofibrillary tangle, NTF), senile plaque formation (senile plaque, SP), and neuron degeneration, and clinical patients often have progressive recognition. Cognitive impairment, memory impairment, and personality change, and eventually developing dementia, once the disease has brought a heavy burden on individuals and families. Because of their high incidence and mortality, and their pathogenesis is not yet clear, it is the focus of research and research by many scholars. It is focused on the expression of A beta protein and Tao protein in the brain and has made great progress. It is well known that the maintenance of various physiological activities of the central nervous system requires high energy supply. However, when various reasons cause the disturbance of energy metabolism, it can affect the normal transmission of synapse information and cause degeneration and loss of neurons. A series of pathological changes, resulting in corresponding symptoms and changes in the body. In recent years, many scholars have explored the pathogenesis and pathological process of AD from the angle of the energy metabolism of the central nervous system. A large number of experimental data have proved that lactic acid can provide energy for the nervous system as a source of energy for neurons, especially as a God. Single carboxylic acids, such as lactic acid, pyruvic acid and ketone body, are playing an important role in the absence of sufficient glucose from the cells and glia cells. The single carboxylic acid transmembrane carrier, monocarboxylate transporter (MCTs), has been proved to be in mammalian brain. There are three subtypes of MCT1, MCT2, and MCT4, of which MCT1, MCT4 is mainly located in astrocytes, and MCT2 is highly expressed in neurons. The three parties coordinate the transport of lactate, pyruvic acid, ketone body and other mono carboxylic substances between glia cells and neurons, mediate the energy metabolism in the brain, and keep the brain in high energy metabolic state in order to maintain the various kinds of energy. Physiological activities. Based on this, we further elaborated the effects and changes of memory changes in the learning of MCTs and AD model mice through a long regular aerobic exercise on AD model mice of different months of age. Objective to explore the changes in the expression of MCT1, MCT2, MCT4 in the brain of AD model mice and to study the changes in the expression of MCT1, MCT2 and MCT4 in the brain of AD model mice. The influence of memory ability. From the point of view of energy metabolism, exercise relates to the development of AD, and provides theoretical basis and experimental data for the pathogenesis of AD and clinical prevention and delay of disease. Methods the experimental group selected the AD model mice of 2,6,10 month old (APP/PS1 double transgenic) and WT wild type mice (C57BL/6J) for 8 weeks. The swimming training was 4,8,12 month old. At the same time, the untrained 4,8,12 month old AD model mice and the WT wild type mice were selected as the control group. First, the Morris water maze was used to detect the behavior (hidden platform and space exploration), and the Western blot was used to detect the expression of MCT1, MCT2, MCT4 protein in the homogenization of brain tissue. The expression of MCT1, MCT2, MCT4 in the cerebral cortex and hippocampal region was observed by immunohistochemistry. Results (1) the results of Morris water maze showed that in the hidden platform experiment, the average escape latency and the escape route of mice after 8 weeks of swimming training were significantly lower than those in the untrained group in the first two days, and the difference was statistically significant (P0.05), and three later. In the space exploration experiment, the time of the 60s internal target quadrant in the training group was significantly higher than that in the untrained mice (P0.05). (2) the protein expression level: (we used Western blot to detect the protein in the brain tissue in 8 month old of the mice). The results showed that the AD model after swimming training was small. The expression of untrained mice and WT mice increased significantly (P0.05). (3) immunohistochemical staining: the expression of MCT1 and MCT4 in the cerebral cortex and hippocampus of the experimental group was higher than that in the control group (P0.05). But there was no significant difference between the MCT2 expression level and the MCT2 expression level. Conclusion the long-term regular aerobic exercise increased the expression of MCTs in the brain of APP/PS1 mice. It improves the energy metabolism of central nervous system and improves learning and memory ability.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.16;R-332
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