| Stereological research suggested that neurons survived in the early stage of AD. The cognitive decline in early stage of AD is closely related to the structure integrity in the white matter. Capillaries plays a vital role in regulating the brain microenvironment and maintaining regional cerebral blood flow and so on. Capillary distribution within the white matter is relatively less dense. Therefore, the white matter is more susceptible to hypoxic-ischemic injury, and capillary injury has a greater impact on the structure and function of white matter. However, there has no study quantitatively investigating the capillary changes in the white matter of transgenic AD mice using the exact three-dimensional quantitative methods. If the neurons did not die, it would be possible for us to look for some ways to prevent or delay the procession of AD. Running exercise has been shown to improve cognition and memory function in AD patients. However the quantitative study on the effects of running exercise on the capillaries in the white matter of early AD has not been found at home and abroad. Tg2576 transgenic AD mice and APP/PS1 transgenic AD mice are the most commonly models used to simulate the animal model of early AD pathology. We used the stereological methods to make accurate three-dimensional quantitative studies on the capillary changes in the white matter of 10-month-old Tg2576 transgenic AD mice and APP/PS1 transgenic AD mice. After the behavioral intervention of transgenic AD mice with running exercise was done, we used the stereological methods to study of the effects of running exercise on the capillaries in the white matter of transgenic AD mice. The present study not only provided the accurate quantitative methods for studying the capillaries in the white matter of transgenic AD mice, but also provided the important structural basis for the protective effects of running exercise on the spatial learning and memory ability of transgenic mouse model of AD.Part one1 Materials and methods1.1 In this study, eleven 10-month-old transgenic AD mice and eleven 10-month-old non-transgenic littermates wild-type mice were randomly selected. The Morris water maze test was used to detect the spatial learning and memory ability in both groups for seven consecutive days. After the behavior test, seven mice from each group were randomly selected. The brains were made into successive 1 mm cerebral slices after anesthesia and infusion. White matter volume was calculated for each mouse with a dissecting microscope and stereological methods.1.2 One side of the hemisphere was randomly selected. With the frozen section techniques, immunohistochemical techniques and stereological techniques, the total volume, total surface area and total length of the capillaries in the white matter were estimated.2 Results2.1 The escape latency of positioning navigation test in Tg2576 transgenic AD mice was significantly longer than that in the same month-old littermate wild-type mice (p< 0.05), while space exploration test showed no significant difference between two groups.2.2 The white matter volume was not significantly different between two groups.2.3 The total volume, total surface area and total length of the capillaries in the white matter of 10-month-old Tg2576 transgenic AD mice (6.90±0.82 m,0.0648±0.0167 mm3,61.77±13.80 mm2) were significantly lower than those in the same month-old littermate wild-type mice (12.44±2.64 m, 0.0891±0.0145 mm3,106.81±20.17 mm2) (p<0.01,p<005,p<0.01).Part two1 Materials and methods1.1 Ten 10-month-old APP/PS1 transgenic AD mice and ten 10-month-old non-transgenic littermates wild-type mice were randomly selected. The spatial learning and memory ability of the mice in both groups were tested with the Morris water maze test. After the behavior test, six mice from each group were randomly selected. The brains were made into successive 1 mm cerebral slices after anesthesia and infusion. White matter volume was calculated for each mouse with a dissecting microscope and stereological methods.1.2 One side of the hemisphere was randomly selected. With the frozen section techniques, immunohistochemical techniques and stereological techniques, the volume of the white matter and the total length, total volume and total surface area of the capillaries in the white matter were estimated.2 Results2.1 Morris water maze behavioral test results showed that the escape latency of positioning navigation test in 10-month-old APP/PS1 transgenic AD mice was significantly longer than that in the same month-old littermate wild-type mice (p< 0.05), and the explore space test of cross platform frequency and quadrant percentage of time results in APP/PS1 double transgenic AD mice were significant decreased compared with the same month old wild-type mice (p<0.05,p<0.05).2.2 The white matter volume of APP/PS1 transgenic AD (11.11±1.05 mm3) were significant decreased compared with the same month old wild-type mice(14.88±0.71 mm3) (p<0.01).2.3. The total length, total volume and total surface area of the capillaries in the white matter of 10-month-old Tg2576 transgenic AD mice (3.90± 0.47 m,0.0364±0.0088 mm3,51.1±4.5 mm2) were significantly lower than those in the same month-old littermate wild-type mice (10.83±1.67 m,0.1062±0.0291 mm3,116.6±16.8 mm2) (p<0.01,p<0.01,p<0.01).Part three1 Materials and methods1.1 Twenty 6-month-old APP/PS1 transgenic AD mice were randomly selected, then randomly divided into two groups, control group and experimental group. With ten mice each group. Four month running exercise intervention was executed for the experimental group. The spatial learning and memory ability of the mice in both groups was tested with the Morris water maze test. After the behavior test, six mice from each group were randomly selected. The brains were made into successive 1 mm cerebral slices after anesthesia and infusion. White matter volume was calculated for each mouse with a dissecting microscope and stereological methods.1.2 One side of the hemisphere was randomly selected. With the frozen section techniques, immunohistochemical techniques and stereological techniques, the total length, total volume and total surface area of the capillaries in the white matter were estimated.2 Results2.1 Morris water maze behavioral test results showed that the escape latency of positioning navigation test in the experimental group AD mice was significantly shorter than that in the control group mice(p<0.05), and the explore space test of cross platform frequency and quadrant percentage of time results in running exercise AD mice were significant increased compared with the control group mice (p<0.05,p<0.05).2.2 The white matter volume of the experimental group AD mice (13.88± 0.83 mm3) were significant increased compared with the control group mice (11.11±1.05 mm3) (p< 0.01).2.3 The total length, total volume and total surface area of the capillaries in the white matter of running exercise group AD mice (7.65±1.75 m, 0.0924±0.0232 mm3,95.0±17.7 mm2) were significantly increased than those in the control group mice (3.90±0.47 m,0.0364±0.0088 mm3,51.1 ±4.5 mm2) (p< 0.01, p< 0.01, p< 0.01).CONCLUSIONS1. This study showed that both Tg2576 transgenic AD male mice and APP/PS1 double transgenic AD male mice appeared behavioral changes in 10 months.2. This study showed that there was no significant change of the white matter volume in 10-month-old Tg2576 transgenic AD male mice. However, the stereological results indicated that there was significant change in the capillaries of the white matter in 10-month-old Tg2576 transgenic AD male mice, which might be one of the important reasons for the early deficient of the spatial learning and memory ability.3. This study showed that the white matter volume of 10-month-old APP/PS1 transgenic AD male mice was significant decreased. The stereological results indicated that there was significant change in the capillaries of the white matter in 10-month-old APP/PS1 transgenic AD male mice, which might be one of the important reasons for the early deficient of the spatial learning and memory ability and the early change of the white matter in the 10-month-old AD mice.4. The capillaries within white matter may serve as an early target for the prevention and treatment of AD.5. This study showed that running exercise could delay the decline of the learning and spatial memory ability in APP/PS1 transgenic AD mice.6. This study showed that the white matter volume of 10-month-old running exercise AD mice was increased significantly. The stereological results indicated that running exercise could delay the decline of the capillaries of the white matter in APP/PS1 transgenic AD mice, improve the role of learning and memory function provides a reference and structural basis. |
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