AD早期行为学、Aβ和白质的改变及跑步锻炼能否延缓这些改变进程的探讨
发布时间：2018-11-24 18:22
【摘要】：第一部分转基因AD小鼠行为学、白质内Aβ及白质结构的早期改变 目的：研究各月龄转基因AD小鼠行为学、白质内Aβ及白质内有髓神经纤维的改变，以期探索早期AD行为学改变的形态学基础，为今后早期诊断及防治AD提供理论依据。 方法：雄性Tg2576转基因小鼠4月龄14只、6月龄14只、8月龄20只和10月龄12只，以及同窝生月龄匹配的雄性野生型小鼠各15只。运用Morris水迷宫进行空间学习、记忆能力的测试，前6天为空间学习、记忆测试，第7天为空间探索能力测试，分别记录动物的寻台时间即潜伏期、动物的穿台次数以及动物在平台所在象限的时间百分比。水迷宫测试结束后，每组小鼠随机选取6只，分离出大脑白质，用ELISA检测每只小鼠大脑白质内Aβ40和Aβ42的含量。从每组剩余小鼠中随机抽取7只，在大脑白质内随机抽取3~4块脑组织块制成电镜标本，运用体视学方法计算转基因AD小鼠大脑白质体积、白质内有髓神经纤维总长度、总体积等体视学参数。 结果：4月龄、6月龄和8月龄转基因AD小鼠与野生型小鼠的空间学习和记忆测试潜伏期均无显著性差异(p0.05)，两组空间探索测试的结果也无显著性差异(p0.05)。10月龄转基因AD小鼠空间学习和记忆测试潜伏期显著性长于野生型小鼠(p 0.05)，两组小鼠的空间探索测试结果不存在显著性差异(p0.05)。4个月龄组的转基因AD小鼠大脑白质内Aβ40浓度均显著性高于各相应月龄组的野生型小鼠(p0.05)，而只有6月龄转基因AD小鼠大脑白质内Aβ42浓度显著性高于野生型小鼠(p 0.05)。10月龄转基因AD小鼠与野生型小鼠白质总体积均无显著性差异(p0.05)；10月龄转基因AD小鼠白质内有髓神经纤维轴突体积显著性小于野生型小鼠(p 0.05)；10月龄转基因AD小鼠与野生型小鼠白质内有髓神经纤维总长度、总体积等体视学参数均无显著性差异(p0.05)。 结论：1.转基因AD小鼠出现空间学习、记忆能力改变的时间大约为10月龄。2.转基因AD小鼠Aβ显著升高的时间为4~6月龄。3.10月龄转基因AD小鼠白质内有髓神经纤维轴突体积的显著性降低，可能是10月龄转基因AD小鼠行为学改变的重要形态学基础之一。 第二部分转基因AD小鼠行为学的早期改变及跑步锻炼对其行为学的影响 目的：研究转基因AD小鼠早期行为学改变，以及跑步锻炼对其行为学改变的影响，以期找到早期AD行为学改变的时间点，为今后早期防治AD的行为学干预手段提供理论依据。 方法：雄性APP/PS1转基因AD小鼠4月龄10只，同窝生4月龄雄性野生型小鼠10只。分别在4月龄、6月龄、8月龄和10月龄时对转基因AD小鼠进行为期7天的Morris水迷宫测试。根据行为学测试结果，在转基因AD小鼠行为学改变之前给予4个月的跑步锻炼干预，然后用Morris水迷宫测试跑步组与对照组转基因AD小鼠的空间学习记忆能力。 结果：转基因AD小鼠在4月龄、6月龄和8月龄时与同月龄野生型小鼠相比，空间学习记忆测试潜伏期均无显著性差异(p0.05)，空间探索测试的结果也无显著性差异(p0.05)。转基因AD小鼠在10月龄时与同月龄野生型小鼠相比，空间学习记忆测试潜伏期显著性长于野生型小鼠(p 0.05)，两组空间探索测试结果无显著性差异(p0.05)。在转基因AD小鼠行为学改变之前（6月龄）给予4个月跑步锻炼干预后，跑步组与对照组转基因AD小鼠相比，，空间学习记忆测试潜伏期显著性缩短(p 0.05)，穿越平台次数和平台所在象限时间百分比均显著性增大(p 0.05)。 结论：在转基因AD小鼠行为学改变之前的跑步锻炼干预，可以延缓转基因AD小鼠空间学习记忆能力的下降。 第三部分跑步锻炼对转基因AD小鼠大脑白质的影响 目的：研究跑步锻炼干预对转基因AD小鼠大脑白质结构改变的影响，以期找到跑步锻炼对转基因AD小鼠行为学改变影响的形态学基础，为今后早期防治AD的行为学和药物手段提供结构基础。 方法：在转基因AD小鼠行为学改变之前（6月龄）给予4个月跑步锻炼干预后，从跑步组和对照组转基因AD小鼠中各随机选取7只，在大脑白质内随机抽取3~4块脑组织块制成电镜标本，运用体视学方法计算每只小鼠大脑白质体积、白质内有髓神经纤维总长度、总体积等体视学参数。 结果：跑步组转基因AD小鼠与对照组相比，大脑白质体积、白质内有髓神经纤维总体积和有髓神经纤维轴突体积均显著性增加(p0.05)，而白质内有髓神经纤维总长度和有髓神经纤维髓鞘总体积均无显著性差异(p0.05)，白质内有髓神经纤维内、外直径和内、外周长均无显著性差异(p0.05)。 结论：1.跑步锻炼可以增加转基因AD小鼠大脑白质体积、白质内有髓神经纤维总体积和有髓神经纤维轴突体积。2.跑步锻炼保护转基因AD小鼠大脑白质结构可能是其延缓转基因AD小鼠空间学习记忆能力下降的重要结构基础之一。
[Abstract]:The early changes of the behavior of the first part of the transgenic AD mice, the white matter A and the white matter structure Objective: To study the behavior of the transgenic AD mice at each age of age, the changes of the white matter in the white matter and the myelinated nerve fibers in the white matter, with a view to exploring the morphology of early AD behavior change. The foundation is to provide a theory for early diagnosis and prevention of AD Methods: 14 of 14-month-old male Tg2576 transgenic mice, 14 at 6-month-old, 20 at 8-month-old and 12 at 10-month-old, and the male wild-type with the same age-of-one-month-old age The space study and memory test were performed using the Morris water maze. The first six days were space study, memory test and space exploration capacity test for the first 6 days. The time of the search for animals, the incubation period, the number of passes of the animals, and the animals in the quadrant of the platform were recorded separately. The time percentage. After the water maze test, 6 mice were randomly selected, and the white matter of the brain was isolated. The white matter of the white matter of each mouse was detected by ELISA. The total length and total volume of the white matter in the white matter of the transgenic AD mice were calculated by stereology. The results showed that there was no significant difference in the latency of spatial learning and memory test of transgenic AD mice at 4 months, 6 months and 8 months with wild-type mice. There was no significant difference between the two groups of space exploration and test (p0.05). The latency of space study and memory test in transgenic AD mice at the age of 10 months was significantly longer than that of wild type. There was no significant difference between the two groups of mice (p0.05). The concentration of A-40 in the white matter of the transgenic AD mice in the 4-month-old group was significantly higher than that of the corresponding one-month-old group. In mice (p0.05), only 6-month-old transgenic AD mice showed a significantly higher concentration of A-42 in the white matter than in wild-type mice (p-0.05). There was no significant difference between the total volume of white matter in transgenic AD mice and wild-type mice at the age of 10 months. In the 10-month-old transgenic AD mice, there was no significant difference in the total length and total volume of the myelinated nerve fibers in the white matter of the 10-month-old transgenic AD mice. iso (p0. Conclusion: 1. The spatial learning and memory ability of transgenic AD mice were changed. The time was about 10-month-old. The time of the significant increase of A-level in the transgenic AD mice was 4-6 months. The significant decrease in the axonal volume of the myelinated nerve fibers in the white matter of the transgenic AD mice at the age of 10 months may be the behavior change of the 10-month-old transgenic AD mice. One of the important morphological bases of the transformation. The early part of the behavior of the second part of the transgenic AD mice The effect of the change and running exercise on the behavior of the transgenic AD mice is to study the changes of the early behavior of the transgenic AD mice and the effect of the running exercise on the behavior of the transgenic AD mice. In order to find the time point of early AD behavior change, it can be used to prevent early AD behavior change. Methods: Male APP/ PS1 transgenic AD mice were 4 months old. Ten male wild-type mice at 4 months of age in the same litter were used for transgenic AD at 4-month, 6-month, 8-and 10-month-old, respectively. The mice were subjected to a 7-day Morris water maze test. Based on the results of the behavior test, a four-month running exercise intervention was given before the behavior change of the transgenic AD mouse, and then the running group was tested with the Morris water maze The spatial learning and memory abilities of the transgenic AD mice in the control group showed no significant difference in the latency of the spatial learning and memory test compared with the wild-type mice at the age of 4, 6 and 8 months (p0.05). There was no significant difference in the results of the space exploration test (p0.05). The latency of the spatial learning and memory test was significantly longer than that of the wild-type mice at the age of 10 months compared to the wild-type mice in the same month (p-0.05). No significant difference was found between the two groups of space exploration tests (p0.05). After four-month running exercise intervention (6 months) before the behavior change of the transgenic AD mice, the running group was compared with the control group transgenic AD mice. The latency of spatial learning and memory test was significantly shortened (p <0.05), and the number of crossing platforms was peaceful. There was a significant increase in the percentage of the quadrant in which the stage was located (p-0.05). Conclusion: Run-forging before the behavior change of the transgenic AD mice can delay the spatial learning and memory ability of the transgenic AD mouse The effect of the third part of running exercise on the white matter of the brain of the transgenic AD mice: the study of the changes of the white matter structure of the brain of the transgenic AD mice by the intervention of running exercise The effect of running exercise on the behavior of transgenic AD mice Based on the morphological basis, a structural basis was provided for the early prevention and treatment of AD behavior and drug means. Methods: After four-month running training intervention (6 months) before the behavior change of the transgenic AD mice, the transgenic AD from the running group and the control group was obtained. 7 of the mice were randomly selected, 3 to 4 blocks of brain tissue were randomly extracted in the white matter of the brain, and a stereological method was used. The total length and total volume of the white matter in the white matter and the total volume of the white matter in each mouse were calculated. Results: The transgenic AD mice of the running group were compared with the control group, and the white body of the brain The total volume of the myelinated nerve fibers in the white matter and the volume of the axon of the myelinated nerve fibers increased significantly (p0.05), while the total length of the myelinated nerve fibers in the white matter and the total volume of the pulp of the myelinated nerve fibers had no significant difference (p0. 05), White There was no significant difference in the inner and outer diameter of the inner and outer diameter of the inner and outer diameter of the nucleus (p0.05). Conclusion: 1. The running exercise can increase the white matter volume of the transgenic AD mouse, the total volume of the myelin in the white matter and the axon volume of the myelinated nerve fiber.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R749.16
本文编号：2354571
[Abstract]:The early changes of the behavior of the first part of the transgenic AD mice, the white matter A and the white matter structure Objective: To study the behavior of the transgenic AD mice at each age of age, the changes of the white matter in the white matter and the myelinated nerve fibers in the white matter, with a view to exploring the morphology of early AD behavior change. The foundation is to provide a theory for early diagnosis and prevention of AD Methods: 14 of 14-month-old male Tg2576 transgenic mice, 14 at 6-month-old, 20 at 8-month-old and 12 at 10-month-old, and the male wild-type with the same age-of-one-month-old age The space study and memory test were performed using the Morris water maze. The first six days were space study, memory test and space exploration capacity test for the first 6 days. The time of the search for animals, the incubation period, the number of passes of the animals, and the animals in the quadrant of the platform were recorded separately. The time percentage. After the water maze test, 6 mice were randomly selected, and the white matter of the brain was isolated. The white matter of the white matter of each mouse was detected by ELISA. The total length and total volume of the white matter in the white matter of the transgenic AD mice were calculated by stereology. The results showed that there was no significant difference in the latency of spatial learning and memory test of transgenic AD mice at 4 months, 6 months and 8 months with wild-type mice. There was no significant difference between the two groups of space exploration and test (p0.05). The latency of space study and memory test in transgenic AD mice at the age of 10 months was significantly longer than that of wild type. There was no significant difference between the two groups of mice (p0.05). The concentration of A-40 in the white matter of the transgenic AD mice in the 4-month-old group was significantly higher than that of the corresponding one-month-old group. In mice (p0.05), only 6-month-old transgenic AD mice showed a significantly higher concentration of A-42 in the white matter than in wild-type mice (p-0.05). There was no significant difference between the total volume of white matter in transgenic AD mice and wild-type mice at the age of 10 months. In the 10-month-old transgenic AD mice, there was no significant difference in the total length and total volume of the myelinated nerve fibers in the white matter of the 10-month-old transgenic AD mice. iso (p0. Conclusion: 1. The spatial learning and memory ability of transgenic AD mice were changed. The time was about 10-month-old. The time of the significant increase of A-level in the transgenic AD mice was 4-6 months. The significant decrease in the axonal volume of the myelinated nerve fibers in the white matter of the transgenic AD mice at the age of 10 months may be the behavior change of the 10-month-old transgenic AD mice. One of the important morphological bases of the transformation. The early part of the behavior of the second part of the transgenic AD mice The effect of the change and running exercise on the behavior of the transgenic AD mice is to study the changes of the early behavior of the transgenic AD mice and the effect of the running exercise on the behavior of the transgenic AD mice. In order to find the time point of early AD behavior change, it can be used to prevent early AD behavior change. Methods: Male APP/ PS1 transgenic AD mice were 4 months old. Ten male wild-type mice at 4 months of age in the same litter were used for transgenic AD at 4-month, 6-month, 8-and 10-month-old, respectively. The mice were subjected to a 7-day Morris water maze test. Based on the results of the behavior test, a four-month running exercise intervention was given before the behavior change of the transgenic AD mouse, and then the running group was tested with the Morris water maze The spatial learning and memory abilities of the transgenic AD mice in the control group showed no significant difference in the latency of the spatial learning and memory test compared with the wild-type mice at the age of 4, 6 and 8 months (p0.05). There was no significant difference in the results of the space exploration test (p0.05). The latency of the spatial learning and memory test was significantly longer than that of the wild-type mice at the age of 10 months compared to the wild-type mice in the same month (p-0.05). No significant difference was found between the two groups of space exploration tests (p0.05). After four-month running exercise intervention (6 months) before the behavior change of the transgenic AD mice, the running group was compared with the control group transgenic AD mice. The latency of spatial learning and memory test was significantly shortened (p <0.05), and the number of crossing platforms was peaceful. There was a significant increase in the percentage of the quadrant in which the stage was located (p-0.05). Conclusion: Run-forging before the behavior change of the transgenic AD mice can delay the spatial learning and memory ability of the transgenic AD mouse The effect of the third part of running exercise on the white matter of the brain of the transgenic AD mice: the study of the changes of the white matter structure of the brain of the transgenic AD mice by the intervention of running exercise The effect of running exercise on the behavior of transgenic AD mice Based on the morphological basis, a structural basis was provided for the early prevention and treatment of AD behavior and drug means. Methods: After four-month running training intervention (6 months) before the behavior change of the transgenic AD mice, the transgenic AD from the running group and the control group was obtained. 7 of the mice were randomly selected, 3 to 4 blocks of brain tissue were randomly extracted in the white matter of the brain, and a stereological method was used. The total length and total volume of the white matter in the white matter and the total volume of the white matter in each mouse were calculated. Results: The transgenic AD mice of the running group were compared with the control group, and the white body of the brain The total volume of the myelinated nerve fibers in the white matter and the volume of the axon of the myelinated nerve fibers increased significantly (p0.05), while the total length of the myelinated nerve fibers in the white matter and the total volume of the pulp of the myelinated nerve fibers had no significant difference (p0. 05), White There was no significant difference in the inner and outer diameter of the inner and outer diameter of the inner and outer diameter of the nucleus (p0.05). Conclusion: 1. The running exercise can increase the white matter volume of the transgenic AD mouse, the total volume of the myelin in the white matter and the axon volume of the myelinated nerve fiber.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R749.16
【参考文献】
相关期刊论文 前2条
1 唐牟尼;对老年期痴呆的流行病学研究[J];国外医学.精神病学分册;1998年02期
2 杨姝;李琛;张伟;汪维伟;唐勇;;大鼠大脑白质及白质内有髓神经纤维老年性改变的体视学研究[J];解剖学报;2007年06期
本文编号：2354571
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