规律运动影响AD模型小鼠脑内单羧酸转运蛋白表达并改善认知功能
发布时间：2018-07-25 17:00
【摘要】：阿尔茨海默病(Alzheimer's disease,AD)是一种常见的、呈进行性发展的、可致死性的中枢神经系统退行性疾病,其病理改变为:神经元纤维缠结(neurofibrillary tangle,NTF)、老年斑形成(senile plaque,SP)以及神经元变性丢失,临床上患者常出现进行性认知障碍、记忆减退以及人格改变,并最终发展为痴呆,一旦罹患此病给个人及家庭都带来了沉重的负担。因其高发病率及致死率的特点,并且其发病机制尚不清楚,所以是广大学者积极探讨和研究的重点。以往对阿尔茨海默病的研究主要集中在对脑内Aβ蛋白和Tao蛋白的表达上,并且取得了很大的进展。众所周知,中枢神经系统各项生理活动的维持,需要高能量供给,然而当各种原因引起能量代谢出现障碍时,则可影响神经突触信息的正常传递,引起神经元变性丢失等一系列病理变化,导致机体出现相应的症状及改变。近几年来,许多学者从中枢神经系统能量代谢的角度来深入探讨AD的发病机制及病变过程。大量的实验数据已经证实了:乳酸可以作为神经元的能量来源为神经系统提供能量,尤其是当神经元和神经胶质细胞不能得到足够的葡萄糖作为能源物质的时候,乳酸、丙酮酸、酮体等单羧酸类物质则发挥着举足轻重的作用。单羧酸类物质跨膜需要载体—单羧酸转运蛋白(monocarboxylate transporter,MCTs)目前,已经证实了在哺乳动物脑内有MCT1、MCT2、MCT4三种亚型,其中MCT1、MCT4主要位于星形胶质细胞,而MCT2则高表达于神经元,三者协同将乳酸、丙酮酸、酮体等单羧酸类物质在胶质细胞和神经元之间进行转运,介导脑内能量代谢,使大脑处于高能量代谢状态以此来维持各项生理活动。基于此我们此次试验通过对不同月龄段的AD模型小鼠进行长时间的规律有氧运动来进一步阐述MCTs与AD模型小鼠学习、记忆改变的影响及变化。目的探讨规律有氧运动对AD模型小鼠脑内MCT1、MCT2、MCT4表达量的改变以及对其学习、记忆能力的影响。从能量代谢的角度将运动与AD的发生、发展联系起来,为以后探讨AD的发病机制以及临床预防、延缓发病提供理论依据及实验数据。方法实验组选择2、6、10月龄的AD模型小鼠(APP/PS1双转基因)和WT野生型小鼠(C57BL/6J),给予8周的游泳训练至4、8、12月龄。同时选择未训练的4、8、12月龄AD模型小鼠和WT野生型小鼠做为对照组。首先采用morris水迷宫对其进行行为学检测(隐蔽平台实验和空间探索实验),采用western blot检测脑组织匀浆中MCT1、MCT2、MCT4蛋白表达水平,采用免疫组织化学观察其大脑皮层和海马区MCT1、MCT2、MCT4表达情况。结果(1)morris水迷宫结果显示:在隐蔽平台实验中,经过8周游泳训练后的小鼠在前两天内较未训练组相比平均逃避潜伏期和逃避路程明显降低,差异具有统计学意义(P0.05),后三天的结果训练组也较未训练组低。在空间探索实验中,训练组小鼠60s内在目标象限停留的时间明显高于未训练组小鼠(P0.05).(2)蛋白表达水平:(我们采用western blot对8月龄的小鼠进行脑组织匀浆蛋白检测)结果提示:游泳训练后的AD模型小鼠和WT小鼠较未训练的表达量显著增加(P0.05)。(3)免疫组织化学染色:实验组中MCT1、MCT4在大脑皮层及海马区的表达较对照组升高(P0.05)。而MCT2表达水平训练前后没有较大的差别。结论长期的规律有氧运动增加了APP/PS1小鼠脑内MCTs表达量,改善了中枢神经系统能量代谢情况,提高了学习、记忆能力。
[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.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.16;R-332
本文编号：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.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.16;R-332
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