| PART ONESTEREOLOGICAL INVESTIGATIONS OF THEAGE-RELATED CHANGES IN THE HIPPOCAMPUS ANDTHE MYELINATED FIBERS IN THE HIPPOCAMPUS OF RATBRAINObjective: To investigate the changes of the hippocampus and themyelinated fibers in the hippocampus of6-month (young),18-month(middle-aged) and28-month (old-aged) female and male rats using newstereological methods in order to further understand how the hippocampusand the myelinated fibers in the hippocampus change during aging process.Methods: Ten young (5female and5male), ten middle-aged (5female and5male) and ten old-aged (5female and5male)Sprague-Dawley (SD) rats were used. Spatial memory was examined withMorris water maze tasks for five consecutive days. Time latency (the totaltime in target quadrant and the target zone frequency) was recorded. Afterthe behavioral tests, five or six hippocampus blocks were sampled in a systematic random fashion. Under electronic microscope with themagnification of7000,15photographs were obtained from eachhippocampus block in a systematic random fashion. The hippocampusvolume, the total volume, total length and mean diameter of the myelinatedfibers in the hippocampus were investigated with the new stereologicalmethods.Results: The time latencies in Morris water maze tasks ofmiddle-aged female and male and old-aged female and male rats was notsignificantly decreased when compared to young female and male rats(p>0.05). The time latencies in Morris water maze tasks of young femaleand middle-aged female rats were significantly longer than those of malerats (p<0.05). There were no significant age-related declines in the volumeof hippocampus, the total length and total volume of the myelinated fibersin the hippocampus. When compared to young and middle-aged femalerats,the total length of the myelinated fibers in the hippocampus of malerats was significantly longer.Conclusions:1. There were significant sex differences in the timelatencies in Morris water maze tasks and the total length of thehippocampal myelinated fibers in young and middle-aged rats.2. The timelatencies of Morris water maze were significantly related to the total lengthof the myelinated fibers in the hippocampus.3. There were no significantage-related changes in the time latencies in Morris water maze tasks and the hippocampal myelinated fibers of aged rats. PART TWOTHE CHANGES OF BEHAVIOR AND MYELINATED FIBERSIN THE HIPPOCAMPUS OF TRANSGENIC MOUSE MODELSOF ADObjective: To investigate the changes of the spatial learning ability,the concentration of Aβ protein, the volume of hippocampus (CA1/DG) andthe myelinated fibers in the hippocampus (CA1/DG) in order toexplore the morphological bases of early AD behavioral changes andprovide theoretical bases for the future target of early diagnosis, earlyprevention and early treatment of AD.Methods:4month-old group (15APPswe and15control mice),6month-old group (15APPswe and15control mice),8month-old group (15APPswe and15control mice) and10month-old group (15APPswe and15control mice) mice were used. A seven consecutive days Morris watermaze was used to examine the spatial learning and memory capacity. Forthe spatial navigation trials from the first to the sixth day, the time latencywas recorded. For the spatial exploratory trials on the seventh day, the totaltime in target quadrant and the target zone frequency were recorded. Afterthe behavioral tests, six mice were randomly sampled from each group. Theconcentration of Aβ protein in hippocampus was investigated with Elisamethod. Then, another five mice were randomly sampled again from eachgroup. Five or six hippocampus blocks (2-3blocks in CA1,2-3blocks in DG) were sampled in a systematic random fashion. Under electronicmicroscope with the magnification of8000and20000,15and10photographs were obtained from each hippocampus block, respectively.The hippocampus volume, the total volume and total length of themyelinated fibers in the hippocampus and the total volume of myelinsheaths of hippocampal myelinated fibers were investigated with the newstereological methods.Results: The spatial navigation trials and spatial exploratory trialsresults in Morris water maze tasks of4month-old group,6month-oldgroup and8month-old group were not significantly changed betweenAPPswe group and control group. The time latency in the spatial navigationtrials of Morris water maze tasks of10month-old APPswe group weresignificantly longer than that of control group (p<0.05), while the total timein target quadrant and the target zone frequency in the spatial exploratorytrials (the7thday) between the two groups of10month-old werenon-significantly different. The concentration of Aβ40protein inhippocampus of the APPswe groups were significantly increased whencompared to the control groups in all age-matched mice (p<0.05). Theconcentration of Aβ42protein in hippocampus of the APPswe group weresignificantly increased from the6month-old when compared to the controlgroup (p<0.05). There were no significant declines in the total length, totalvolume of the myelinated fibers and the total volume of the myelin sheaths in the hippocampus (CA1) of APPswe group. When compared to that ofcontrol group,the total length of the myelinated fibers in DG of APPswegroup was significantly lower; however, the total volume of the myelinatedfibers and total volume of the myelin sheaths of the myelinated fibers werenot significantly declined.Conclusions:1. The time for the transgenic mouse model of AD tohave behavioral deficits was around10months.2. The time for thetransgenic mouse model of AD to have significant high concentration of Aβprotein was from4months to6months.3. When compared to that ofcontrol group,the total length of the myelinated fibers in DG of10monthtransgenic mouse model of AD was significantly lower, which might bethe morphological bases for the behavioral deficts of10month transgenicmouse models of AD.
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