AD早期行為學、Aβ和白質(zhì)的改變及跑步鍛煉能否延緩這些改變進程的探討
發(fā)布時間：2018-11-24 18:22
【摘要】：第一部分轉(zhuǎn)基因AD小鼠行為學、白質(zhì)內(nèi)Aβ及白質(zhì)結(jié)構(gòu)的早期改變 目的：研究各月齡轉(zhuǎn)基因AD小鼠行為學、白質(zhì)內(nèi)Aβ及白質(zhì)內(nèi)有髓神經(jīng)纖維的改變，以期探索早期AD行為學改變的形態(tài)學基礎(chǔ)，為今后早期診斷及防治AD提供理論依據(jù)。 方法：雄性Tg2576轉(zhuǎn)基因小鼠4月齡14只、6月齡14只、8月齡20只和10月齡12只，以及同窩生月齡匹配的雄性野生型小鼠各15只。運用Morris水迷宮進行空間學習、記憶能力的測試，前6天為空間學習、記憶測試，第7天為空間探索能力測試，分別記錄動物的尋臺時間即潛伏期、動物的穿臺次數(shù)以及動物在平臺所在象限的時間百分比。水迷宮測試結(jié)束后，每組小鼠隨機選取6只，分離出大腦白質(zhì)，用ELISA檢測每只小鼠大腦白質(zhì)內(nèi)Aβ40和Aβ42的含量。從每組剩余小鼠中隨機抽取7只，在大腦白質(zhì)內(nèi)隨機抽取3~4塊腦組織塊制成電鏡標本，運用體視學方法計算轉(zhuǎn)基因AD小鼠大腦白質(zhì)體積、白質(zhì)內(nèi)有髓神經(jīng)纖維總長度、總體積等體視學參數(shù)。 結(jié)果：4月齡、6月齡和8月齡轉(zhuǎn)基因AD小鼠與野生型小鼠的空間學習和記憶測試潛伏期均無顯著性差異(p0.05)，兩組空間探索測試的結(jié)果也無顯著性差異(p0.05)。10月齡轉(zhuǎn)基因AD小鼠空間學習和記憶測試潛伏期顯著性長于野生型小鼠(p 0.05)，兩組小鼠的空間探索測試結(jié)果不存在顯著性差異(p0.05)。4個月齡組的轉(zhuǎn)基因AD小鼠大腦白質(zhì)內(nèi)Aβ40濃度均顯著性高于各相應(yīng)月齡組的野生型小鼠(p0.05)，而只有6月齡轉(zhuǎn)基因AD小鼠大腦白質(zhì)內(nèi)Aβ42濃度顯著性高于野生型小鼠(p 0.05)。10月齡轉(zhuǎn)基因AD小鼠與野生型小鼠白質(zhì)總體積均無顯著性差異(p0.05)；10月齡轉(zhuǎn)基因AD小鼠白質(zhì)內(nèi)有髓神經(jīng)纖維軸突體積顯著性小于野生型小鼠(p 0.05)；10月齡轉(zhuǎn)基因AD小鼠與野生型小鼠白質(zhì)內(nèi)有髓神經(jīng)纖維總長度、總體積等體視學參數(shù)均無顯著性差異(p0.05)。 結(jié)論：1.轉(zhuǎn)基因AD小鼠出現(xiàn)空間學習、記憶能力改變的時間大約為10月齡。2.轉(zhuǎn)基因AD小鼠Aβ顯著升高的時間為4~6月齡。3.10月齡轉(zhuǎn)基因AD小鼠白質(zhì)內(nèi)有髓神經(jīng)纖維軸突體積的顯著性降低，可能是10月齡轉(zhuǎn)基因AD小鼠行為學改變的重要形態(tài)學基礎(chǔ)之一。 第二部分轉(zhuǎn)基因AD小鼠行為學的早期改變及跑步鍛煉對其行為學的影響 目的：研究轉(zhuǎn)基因AD小鼠早期行為學改變，以及跑步鍛煉對其行為學改變的影響，以期找到早期AD行為學改變的時間點，為今后早期防治AD的行為學干預手段提供理論依據(jù)。 方法：雄性APP/PS1轉(zhuǎn)基因AD小鼠4月齡10只，同窩生4月齡雄性野生型小鼠10只。分別在4月齡、6月齡、8月齡和10月齡時對轉(zhuǎn)基因AD小鼠進行為期7天的Morris水迷宮測試。根據(jù)行為學測試結(jié)果，在轉(zhuǎn)基因AD小鼠行為學改變之前給予4個月的跑步鍛煉干預，然后用Morris水迷宮測試跑步組與對照組轉(zhuǎn)基因AD小鼠的空間學習記憶能力。 結(jié)果：轉(zhuǎn)基因AD小鼠在4月齡、6月齡和8月齡時與同月齡野生型小鼠相比，空間學習記憶測試潛伏期均無顯著性差異(p0.05)，空間探索測試的結(jié)果也無顯著性差異(p0.05)。轉(zhuǎn)基因AD小鼠在10月齡時與同月齡野生型小鼠相比，空間學習記憶測試潛伏期顯著性長于野生型小鼠(p 0.05)，兩組空間探索測試結(jié)果無顯著性差異(p0.05)。在轉(zhuǎn)基因AD小鼠行為學改變之前（6月齡）給予4個月跑步鍛煉干預后，跑步組與對照組轉(zhuǎn)基因AD小鼠相比，，空間學習記憶測試潛伏期顯著性縮短(p 0.05)，穿越平臺次數(shù)和平臺所在象限時間百分比均顯著性增大(p 0.05)。 結(jié)論：在轉(zhuǎn)基因AD小鼠行為學改變之前的跑步鍛煉干預，可以延緩轉(zhuǎn)基因AD小鼠空間學習記憶能力的下降。 第三部分跑步鍛煉對轉(zhuǎn)基因AD小鼠大腦白質(zhì)的影響 目的：研究跑步鍛煉干預對轉(zhuǎn)基因AD小鼠大腦白質(zhì)結(jié)構(gòu)改變的影響，以期找到跑步鍛煉對轉(zhuǎn)基因AD小鼠行為學改變影響的形態(tài)學基礎(chǔ)，為今后早期防治AD的行為學和藥物手段提供結(jié)構(gòu)基礎(chǔ)。 方法：在轉(zhuǎn)基因AD小鼠行為學改變之前（6月齡）給予4個月跑步鍛煉干預后，從跑步組和對照組轉(zhuǎn)基因AD小鼠中各隨機選取7只，在大腦白質(zhì)內(nèi)隨機抽取3~4塊腦組織塊制成電鏡標本，運用體視學方法計算每只小鼠大腦白質(zhì)體積、白質(zhì)內(nèi)有髓神經(jīng)纖維總長度、總體積等體視學參數(shù)。 結(jié)果：跑步組轉(zhuǎn)基因AD小鼠與對照組相比，大腦白質(zhì)體積、白質(zhì)內(nèi)有髓神經(jīng)纖維總體積和有髓神經(jīng)纖維軸突體積均顯著性增加(p0.05)，而白質(zhì)內(nèi)有髓神經(jīng)纖維總長度和有髓神經(jīng)纖維髓鞘總體積均無顯著性差異(p0.05)，白質(zhì)內(nèi)有髓神經(jīng)纖維內(nèi)、外直徑和內(nèi)、外周長均無顯著性差異(p0.05)。 結(jié)論：1.跑步鍛煉可以增加轉(zhuǎn)基因AD小鼠大腦白質(zhì)體積、白質(zhì)內(nèi)有髓神經(jīng)纖維總體積和有髓神經(jīng)纖維軸突體積。2.跑步鍛煉保護轉(zhuǎn)基因AD小鼠大腦白質(zhì)結(jié)構(gòu)可能是其延緩轉(zhuǎn)基因AD小鼠空間學習記憶能力下降的重要結(jié)構(gòu)基礎(chǔ)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.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R749.16
本文編號：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.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R749.16
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本文編號：2354571
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