| PART ONE STEREOLOGICAL STUDY OF THE CHANGES OF THE MYELINATED NERVE FIBERS AND THE OLIGODENDROCYTES IN THE DENTATE GYRUS OF THE AGED APP/PS1 TRANSGENETIC MICEObjective: To investigate the changes of the myelinated nerve fibers in the dentate gyrus(DG) of the 16-month-old male APP/PS1 transgenetic model mice using the unbiased stereological methods in order to further understand the morphological changes in the hippocampus of the Alzheimer’s disease.Methods: In this study, seven 16-month-old male APP/PS1 mice and seven 16-month-old male wild-type mice were randomly selected. The spatial learning and memory abilities of the 16 month-old male APP/PS1 mice and wild-type mice were investigated using the Morris Water Maze test. Then the mice were killed under anaesthesia, one side hemisphere of each mouse brain was selected randomly and three or four tissue blocks were taken out from the sampled hemisphere to be used for the preparation of the translation electron microscopy. The total volume of DG and the parameters of the myelinated nerve fibers within the DG(including the total length, the total volume, the external and internal diameter of the myelinated fibers) were obtained using the unbiased stereological methods. The other side hemisphere of each mouse brain was processed for 50 μm isotropic continuous frozen sections.The oligodendrocytes were immunohistochemically labeled with CNPase antibody. Then, the number of CNPase-positive cells in the dentate gyrus of the hippocampus was estimated with the stereological methods.Results: Morris Water Maze results showed that the escape latency of the AD mice was significantly longer than that of the wild-type mice(group effect: p = 0.008, F = 9.952; time effect: p = 0.023, F = 3.082; time group interaction: p = 0.873, F = 0.312). The target zone frequency and the time in target quadrant zone in the probe trial task of the AD mice were significantly decreased compared with that of the wild-type(p = 0.011, t =-3.008; p = 0.002, t =-3.887). The hippocampal volume and the dentate gyrus volume were not significantly different between the AD mice and the wild-type mice. However, the myelin sheaths of the myelinated fibers in the DG of both group mice existed degenerative changes. Moreover, the stereological results showed that the total length of the myelinated fibers with the diameter range from 0.5 to 1.1 μm in the DG of the AD mice was significantly decreased when compared to that of the wild-type mice(p = 0.049, t =-2.192). Besides, there was no significant difference in the total number of the oligodendrocytes in the dentate gyrus between the two groups(p = 0.282,t = 1.154).Conclusions: The spatial learning and memory abilities of the 16-month-old male APP/PS1 AD mice were decreased significantly when compared to the wild-type mice. The significant loss of the myelinated fibers with the diameter range from 0.5 to 1.1 μm in the DG of the APP/PS1 AD mice might be one of the structural bases for the memory and learning deficits of the old APP/PS1 model mice.PART TWO THE EFFECTS OF RUNNING EXERCISE ON THE MYELINATED NERVE FIBERS AND THE OLIGODENDROCYTES IN THE DENTATE GYRUS OF THE AGED APP/PS1 TRANSGENETIC MICEObjective: To investigate whether treadmill exercise could delay the progress of the learning and memory dysfunction of aged APP / PS1 double transgenic mice. If treadmill exercise could enhance the learning and memory ability of aged APP / PS1 double transgenic mice, then whether exercise plays the role through affecting the myelinated fibers and oligodendrocytes in the dentate gyrus of the brain.Methods: Fourteen male APP / PS1 double transgenic mice were selected at the age of 12 months and then they were randomly divided into running AD group and model control group with seven mice in each group. For running group, the treadmill exercise was conducted at a speed of 10 m/min, for 20 mins each day, 5 days per week, for 4 months. After running, the mouse behavioral was tested using Morris water maze and then they were killed under anesthesia, one side hemisphere of each mouse brain was selected randomly and three or four tissue blocks were taken out from the sampled hemisphere to be used for the preparation of the translation electron microscopy. The total volume of DG and the parameters of the myelinated nerve fibers within the DG(including the total length, the total volume, the external and internal diameter of the myelinated fibers) were obtained using the unbiased stereological methods. The other side hemisphere of each mouse brain was processed for 50 μm isotropic continuous frozen sections. The oligodendrocytes were immunohistochemically labeled with CNPase antibody. Then, the number of CNPase-positive cells in the dentate gyrus of the hippocampus was estimated with the unbiased stereological methods..Results: Morris water maze test showed that there was no significant differencein the escape latency of both groups in the hidden platform trials between the two groups(group effect: p = 0.200, F = 1.837; time effect: p = 0.023, F = 3.644; group time interaction: p = 0.282, F = 1.326). The target zone frequency in the probe trial task of both groups was not significantly different(p = 0.315, t = 1.075), but the time in target quadrant zone of running AD group was significantly longer than that of the model AD group(p = 0.015, t = 2.823). Compared with the model AD group, the volume of DG, the volume of myelinated nerve fibers, the volume of axons of the myelinated nerve fibers, the volume of the myelin sheathes of the myelinated nerve fibers, the total length of the myelinated nerve fibers in DG of running AD group were not significantly different, but the total length of the myelinated fibers with the diameter range from 0.2 to 0.7 μm in the DG of running AD group was significantly longer than the model AD group(p = 0.023, t = 2.598). In addition, compared with the model AD group, the number of CNPase-positive cells in DG of the running AD group was not significantly different(p = 0.220, t =-1.331).Conclusion: Four months treadmill exercise could improve the spatial memory ability of the 16-month-old APP / PS1 mice to some extent and it also could protect the myelinated fibers with the diameter range from 0.2 to 0.7 μm in the DG of the APP/PS1 model mice significantly. |
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