| With the acceleration of the aging process, Alzheimer's disease(AD), a kind of high incidence disease, has received the widespread attention in the world. However, there are still no effective treatments that can prevent, impede, or reverse Alzheimer's disease. Currently, running exercise as a means of behavior to delay the cognition decline has been widely concerned. Even though a lot of previous studies on AD focused on the grey matter changes in AD, but imaging study showed that the white matter volume of AD patients was decreased. It has been reported that the pathological changes of the white matter in AD included decreasing myelin density and demyelination. Whether exercise could also have effect on the white matter changes of AD? If exercise has positive effect on the white matter changes of AD, whether exercise has positive effect on the myelinated nerve fibers in the white matter of AD? All these issues have not been investigated yet. Therefore, in the previous study, six-month-old female APP/PS1 double transgenic mouse model of AD were given four month running exercise intervention. After running exercise, Morris water maze test was used to detect the spatial learning and memory abilities of the mice from the both groups. The white matter volume, the total length and total volume of the myelinated fibers in the white matter, the total volume of the myelin sheaths and the total volume of the axons in the white matter were investigated with the accurate three-dimensional quantitative stereological methods. The present results would be helpful for us to find a more appropriate starting point to search for a variety of means to prevent and treat AD in the future.Part One3.1. Materials and methods1.1 6-month-old female APP/PS1 transgenic mice, were randomly divided into the control group (n= 7) and the running group (n= 12). The running group went through 4 months of running exercise training, at a speed of 10 m/min for 20 min/day and 5 day/week. The first week is the adaptation period, exercised mice ran at a speed of 5 m/min for 10 min/day. From the second week, the mice continued to running at a speed of 10 m/min for 20 min/day. The control group did not run.1.2 After running exercise, Morris water maze test was used to detect the spatial learning and memory abilities of the mice from the both groups.2. ResultsFor place navigation test, the mean escape latency of the running group from day 1 to day 6 was significantly shortened when compared to the contol group (P< 0.05). On the 7th day, for spatial probe test, the target zone frequency and the percentage of time in target quadrant of the running group in spatial probe test were significantly increased when compared to the control group (P< 0.01, P< 0.01).Part two1. Materials and methods1.1 After Morris water maze, senven mice were randomly picked up from each group. One of the two hemispheres from each mouse was selected for experiment. Each hemisphere was cut into 1 mm thick slabs along the coronal direction. Each brain slice was photographed. The anatomy microscope image of one brain slice(anatomy microscope, × 35). The total volume of the white matter was was be calculated using the Cavalieri's principle.1.2 From each hemisphere,3 to 4 white matter blocks with the size of 1 mm3 were sampled in the places where the points in that point grid hit white matter. One section about 60 nm-thickness was cut from each epon block by an ultramicrotome and viewed in a transmission electron microscope. Ten fields of vision were randomly chosen and photographed at a magnification of 8000 or 20000 from each section.1.3 The white matter volume, the total length and total volume of the myelinated fibers in the white matter, the total volume of the myelin sheaths and the total volume of the axons in the white matter were investigated with the quantitative stereological methods.2. Results2.1 After four month treadmill exercise intervention, compared with the white matter volume of the control group, the white matter volume of the running group was significantly increased (P< 0.05).2.2 After four month exercise, the total volume of the myelinated fibers and the axons in the white matter of the running group were significantly increased when compared to the control group (P< 0.05, P< 0.05).2.3 The total length of the myelinated fibers and the total volume of the myelinated sheaths in the white matter were not significantly different between the two groups (P> 0.05).2.4 The mean diameter of the axons in the myelinated fibers of the white matter of the running group were significantly increased when compared to the control group (P< 0.05).2.5 There was no significant difference in the outer diameter, outer perimeter, inner perimeter of myelin sheaths; thickness of myelin sheaths of the myelinated nerve fibers in the white matter between the two groups (P >0.05).General conclusions1. This study further confirmed that running exercise intervention could delay the decline in the cognitive function in early AD.2. Combining the method of transmission electron microscopy with stereological methods, the changes of the myelinated fibers of 6-month-old female APP/PS1 transgenic mice were accurately quantitatively measured after 4-months running exercise, acquiring the white matter volume, the total volume and the total length of the myelinated fibers, the total volume of the axons and myelinated sheath in the white matter, which will provides an important reference for the similar researches in the future.3. When compared to the control group, the white matter volume, the total volume of the myelinated fibers and the total volume of the axons in the white matter of the running group were significantly increased. The total length of myelinated fibers and the total volume of myelinated sheath in the white matter were not statistically different between the two groups. The mean diameter of axons of myelin sheaths in the myelinated fibers of the white matter of the running group were significantly increased when compared to the control group. |
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