The Early Changes Of Behavior And Amyloid And The White Matter In Alzheimer’s Disease And The Effects Of Exercise On The Behavior And The White Matter In Alzheimer’s Disease

PART ONETHE EARLY CHANGES OF BEHAVIOR AND AMYLOID AND THEWHITE MATTER IN THE TRANSGENIC MOUSE MODEL OFALZHEIMER’S DISEASEObjective: To investigate the early changes of the spatial learningability, the concentration of Aβ and the myelinated fibers of the whitematter in the transgenic mouse model of Alzheimer’s disease in order toexplore the morphological basis for behavioral changes in early AD andprovide theoretical basis for early diagnosis and prevention of AD in thefuture.Methods: Male Tg2576transgenic mice were divided into4-month-oldgroup (14mice),6-month-old group (14mice),8-month-old group (20mice) and10-month-old group (12mice);15month-matched littermatewild-type male mice in each group. The spatial learning and memory were examined with Morris water maze for seven consecutive days. From thefirst to the sixth day, the time latency was recorded for the spatial learningand memory capability. On the seventh day, the target zone frequency andthe percentage of time in target quadrant zone were recorded for the spatialexploration capability. After the Morris water maze,6mice were randomlysampled from each group and the white matter was isolated. Theconcentration of Aβ40and Aβ42in the white matter were detected byELISA test. Then,7mice were randomly sampled from each group. Threeor four tissue blocks were randomly sampled from each white matter formaking electron microscopy specimens. The white matter volume, the totallength and the total volume of myelinated fibers in the white matter wereinvestigated with the stereological methods.Results: The results of the spatial navigation trials and the spatialexploratory trials of4-month-old group,6-month-old group and8-month-old group were not significantly different between wild-typegroup and Tg2576group (p>0.05). The time latency in the spatialnavigation trials of10-month-old Tg2576group were significantly longerthan that of wild-type group (p <0.05). The results of the spatialexploratory trials of10-month-old group were not significantly differentbetween wild-type group and Tg2576group (p>0.05). The concentrationof Aβ40in the white matter of each Tg2576group was significantlyincreased when compared to the wild-type group in month-matched mice (p <0.05). The concentration of Aβ42in the white matter of6-month-oldTg2576group was significantly increased when compared to the wild-typegroup in month-matched mice (p <0.05), while that of the4-month-oldgroup,8-month-old group and10-month-old group were not significantlydifferent when compared to the month-matched wild-type mice (p>0.05).In10-month-old mice, the white matter volume, the myelinated fiber length,the myelinated fiber volume and the myelin sheath volume in the whitematter were not significantly different between wild-type mice and Tg2576transgenic mice (p>0.05), however, the axon volume in the white matter ofthe Tg2576transgenic mice was significantly decreased when compared tothe wild-type mice (p>0.05).Conclusions:1.10-month-old transgenic AD mice started to appearbehavioral changes.2. Aβ content in the white matter started tosignificantly increase in4to6month old transgenic AD mice.3. The axonvolume in the myelinated fibers of the white matter in the10-month-oldtransgenic AD mice was significantly increased when compared to thewild-type mice, which might be one of the morphological bases for thebehavioral deficits of the10-month-old transgenic mouse model of AD. PART TWOTHE EARLY CHANGES OF BEHAVIOR AND THE EFFECTS OFEXERCISE ON THE BEHAVIOR IN THE TRANSGENIC MOUSEMODEL OF ALZHEIMER’S DISEASEObjective: To investigate the early changes of behavior and the effectsof exercise on the behavior in the transgenic mouse model of Alzheimer’sdisease in order to find out the time of the behavioral changes in early ADand provide theoretical basis for early behavioral intervention prevention ofAD in the future.Methods: Ten male4-month-old APP/PS1transgenic mice and ten male4-month-old male littermates wild-type mice were used. The spatiallearning and memory of the transgenic AD mice were examined withMorris water maze for seven consecutive days in4-month-old mice,6-month-old mice,8-month-old mice and10-month-old mice, respectively.According to the behavioral test results, four month running exerciseintervention was executed before the behavioral changes in APP/PS1transgenic mice appeared. Then, the spatial learning and memory abilitiesof control group and running group in transgenic AD mice were tested withMorris water maze test.Results: The results of the spatial navigation trials and the spatialexploratory trials of4-month-old group,6-month-old group and 8-month-old group were not significantly different between wild-typegroup and APP/PS1group (p>0.05). The time latency in the spatialnavigation trials of10-month-old APP/PS1group were significantly longerthan that of wild-type group (p <0.05). The results of the spatialexploratory trials of10-month-old group were not significantly differentbetween wild-type group and APP/PS1group (p>0.05). After4monthrunning intervention, the time latency in the spatial navigation trials ofrunning group was significantly shorter than that of control group (p <0.05).The target zone frequency and the percentage of time in target quadrantzone in the spatial exploratory trials of running group were significantlyincreased (p <0.05).Conclusions: The running exercise intervention before the time of thebehavioral changes could delay the learning and memory decline inAPP/PS1transgenic mouse model of AD. PART THREETHE EFFECTS OF EXERCISE ON THE WHITE MATTER IN THETRANSGENIC MOUSE MODEL OF ALZHEIMER’S DISEASEObjective: To investigate the effects of exercise on the white matter inthe transgenic mouse model of Alzheimer’s disease in order to find out themorphological basis of the effects of exercise on behavioral changes intransgenic AD mouse and provide structural basis for early behavioralintervention and drug prevention of AD in the future.Methods: Four month running exercise intervention was executedbefore the behavioral changes in APP/PS1transgenic mice appeared. Then,7mice were randomly sampled from each group. Three or four tissueblocks were randomly sampled from each white matter for making electronmicroscopy specimens. The white matter volume, the total length and thetotal volume of myelinated fibers in the white matter were investigatedwith the stereological methods.Results: When compared to the control group, the white matter volume,the total volume of the myelinated fibers and the total volume of the axonsin running group were significantly increased (p <0.05); the total length ofthe myelinated fibers and the total volume of myelin sheaths in runninggroup were not significantly different (p>0.05); the inner diameter andouter diameter, the inner perimeter and outer perimeter of myelin sheaths in running group were not significantly different (p>0.05).Conclusions:1. Exercise could increase the white matter volume, thetotal volume of the myelinated fibers and the total volume of the axons inthe white matter of transgenic AD mice.2. The protective effects ofexercise on the myelinated fibers in the white matter of AD mice might beone of the structure bases for the protective effects of exercise on thelearning and memory decline in AD.