| Background:Since Alzheimer’s disease was first proposed, there has been more than a century. Among this, the international neuroscience community has carried out a lot of exploration and research, bu tits etiology and pathogenesis remains unclear. β-amyloid protein as one of the four major pathological manifestations ofAD,is considered to be a common pathway which involved in the pathogenesis of several other mechanisms. Aβ can participate in AD pathology through many ways, so how to promote Aβ clearance effectively has become an important target for clinical treatment of AD.Though the existing drugs against Aβ can clearAβ, but also generates a lot of side effects,thus looking for a non-invasive means which can effectively prevent or alleviate AD is particularly important.Recent studies have confirmed that exercise as an europrotective strategy can effectively delay the pathological process of AD, improve spatial learning and memory ablity.Objective:This study take APP/PS1 transgenic mice as the research object, then give 16 weeks of wheel running exercise intervention from 3 months of age, to explore the effect of exercise on spatial learning and memory, hippocampal Aβ deposition levels and microglial phagocytosis of Ap in APP/PS1 transgenic mice, and explain the effect on spatial learning and memory and the cellular mechanisms of Aβ endocytosis clearance in APP/PS1 transgenic mice.Methods:22 3-month-old APP/PS1 mice were randomly divided into 2 groups: transgenic control group (TC, n=11) and transgenic exercise group (TE, n=11); while 22 normal wild-type same age, same germline C57BL/6 mice were randomly divided into wild-type control group (C, n=11)and wild-type exercise group(E, n=11).Wherein, E group and TE group were given normal drinking water and diet, but also carried out 16 weeks of wheel running exercise. After exercise, in the first 17 weeks we use Morris water maze behavioral experiments to detect spatial learning and memory of each.24h after Morris water maze test, all mice derived according to the required method, then performed index test. PT-PCR to detect the transcription levelof TGF-β1, TGF-β1R Ⅱ, CDllb, SR-A Ⅰ, CD68 and CD206 in hippocampus; immunofluorescence test to detect microglia quantity, A8 deposition levels and the coexistence of microglia and AP in hippocampus.Results:(1) In place navigation test, compared with group C, the latency and total distance of E mice were significantly reduced, while the latency and total distance of TC mice were higher than group C mice; compared with the TC group, latency and total distance of TE mice were significantly reduced. In spitial probe test, compared with group C, the number of cross platform of E group were significantly increased, while the total distance, the number of cross platforms and initial crossing angle in radians of TC mice were significantly reduced; compared with TC group, the total distance of TE mice, the percentage of time and distance quadrant, the number of cross platforms and initial crossing angle in radians were significantly increased.(2) Compared with group C, the hippocampus of Aβ deposition levels of E group were significantly lower, while Aβ deposition in hippocampus of mice significantly increased levels of TC; compared with TC group, hippocampal Aβ deposition level TE group were significantly lower, with a very significant difference.(3) Compared with group C, the number of positive microglia CD11b E hippocampus of mice was significantly reduced, with a very significant difference, and the number of hippocampal CD11b TC mice positive microglial cells, CD11b and CD68 in gene transcription were significantly higher in the water, and CD206, CD206/CD68 ratio decreased significantly; compared with the TC group, the number of mice hippocampus CD11b TE positive microglial cells, CD11b and CD68 gene transcript levels were significantly lower, and CD206, the ratio of CD206/CD68 was significantly increased.(4) Compared with group C, TC mice hippocampal gene transcription levels of TGF-β1 significantly increased, with a significant difference, and TGF-β1R Ⅱ of mRNA levels were significantly decreased, with a very significant difference; and TC group Compared, TE mice hippocampal gene transcription levels of TGF-β1 decreased significantly, with a very significant difference, and TGF-β1R Ⅱ of mRNA levels were significantly increased, with a very significant difference.(5) Compared with group C, TC group mouse hippocampus SR-A I transcript levels were significantly lower, with a significant difference; compared with the TC group, TE group mouse hippocampus SR-A I transcript levels were significantly increased, with significant differences.Conclusions:(1) APP/PS1 transgenic mice showed damage on spatial learning and memory functions, and 16 weeks of wheel running exercise can effectively alleviate the decline of their cognitive function, improved spatial learning and memory.(2) APP/PS1 transgenic mouse hippocampus of AP deposition increased significantly, and 16 weeks of wheel running exercise can significantly lower APP/PS1 transgenic mouse hippocampus of Aβ deposition.(3) APP/PS1 transgenic mouse hippocampus seen clearly microglial proliferation and activation, and 16 weeks of wheel running exercise can inhibit microglia proliferation and are able to inhibit movement M1 type microglia activation, and promote M2 type microglia activation.(4) There is a TGF-β1 signaling pathway conduction disorderin APP/PS1 transgenic mouse brain, and 16 weeks of wheel running exercise can enhanceTGF-β1 signaling pathway through increasing the level of TGF-β1R Ⅱ gene transcription.(5) APP/PS1 transgenic mouse hippocampus showed lower level of SR-A I, and the 16 weeks of wheel running exercise can increase mouse hippocampus SR-A I gene transcription level, thereby enhancing the microglial phagocytosis and clearance role on Aβ. |
PDF Full Text Request