| Alzheimer’s disease is a neurodegenerative disease with high disability and death rate among the elderly.It is characterized by progressive memory deficits and other cognitive disturbances,and deterioration of language and conduct.Extracellular abnormal accumulation of Aβ is a major factor of AD,AD neuro-vascular hypothesis states that the damage of cerebral microvascular A(3 transport protein such as low density lipoprotein receptor related protein and P-gp leads to impaired clearance of Aβ,which will cause abnormal accumulation of Aβ and induce AD subsquently.The P-gp transport protein plays a critical role in Aβ clearance,which is the product of the downstream in Wnt/β-catenin signaling.Recent evidences indicate that exercise can reduce the risk of AD by enhancing the rate of Aβ clearance from the brain.Therefore,this research will explore the effect of exercise on Aβ transportation and Wnt/β-catenin signaling pathway in Tg APP/PS1 mice,which may become a new view for the prevention of AD.Objective:3 month old Tg APP/PS1 mice were chosen as experimental animal models and were subjected to moderate intensity of treadmill exercise for 12 weeks,aiming to explore the effects of moderate intensity of treadmill exercise on Aβ transport in hippocampus of Tg APP/PS1 mice Hoping to elaborate the possible molecular mechanism of Aβ transportation from aspects of the hippocampus Wnt/β-catenin signaling pathway and Aβ transport protein expression.Methods:3 month old Tg APP/PS1 mice were divided into the transgenic exercise group(Transgenictype exercise,TG-EXE,N=18)and the transgenic sedentary group(Transgenic type Sed,TG-Sed group,N=18)randomly.3 month old control(Wild)mice were also divided into the wild-type exercise group(Wild type exercise,WT-EXE,N=18)and the wildtype sedentary group(Wild type sedentary,WT-Sed,N=18)randomly.Mice in WT-EXE group and TG-EXE group were subjected to treadmill exercise intervention for 12 weeks.Mice in WT-Sed group and TG-Sed group were sedentary.Then,6 mice of each group were randomly selected to perform 0.9%Nacl perfusion and brains were fixed in 4%paraformaldehyde using paraffin section to perform the immunohistochemical experiments;6 mice of each group were sacrificed to isolate bilateral hippocampus for RT-PCR and Elisa test;The remaining 6 mice were sacrificed to collect bilateral hippocampus for Western Blotting.This research tests the mRNA expressions,protein and Aβ plaques number using Western Blotting,immunohistochemical experiments,RT-PCR and Elisa.Results:(1)Compared with WT-Sed group,The Aβ40(P<0.01)and Aβ42(P<0.01)content and Aβ plaques number(P<0.01)in hippocampus of 7 months old Tg APP/PS1 mice increased significantly,12weeks of moderate intensity of treadmill exercise significantly reduced Aβ40(P<0.05)and Aβ42(P<0.05)content as well as the Aβplaques number(P<0.05).(2)Compared with WT-Sed group,the protein and mRNA of transport protein such as LRP1(P<0.01)and P-gp(P<0.01)in hippocampus of 7 months old Tg APP/PS1 mice decreased significantly.12 weeks of moderate intensity of treadmill exercise significantly increased LRP1 and P-gp(P<0.01)mRNA and protein expression level.(3)Compared with WT-Sed group,the mRNA expression level of CK1(P<0.05)and the activation of GSK3β(P<0.05)in hippocampus of 7 months old Tg APP/PS1 mice increased significantly.Compared with TG-Sed group,12 weeks of moderate intensity of treadmill exercise significantly increased Wnt3a mRNA and protein expression levels and Axin2(P<0.05)mRNA expression level in hippocampus of Tg APP/PS1 mice,however,APC(P<0.01),CK1(P<0.01)mRNA expression level and activation of GSK3β decreased significantly.Conclusions:(1)Moderate intensity treadmill exercise decreased Aβ content and A(3 plaques number by increasing the expression of P-gp and LRP-1 in hippocampus of Tg APP/PS1 mice.(2)Moderate intensity treadmill exercise increased the expression of P-gp and LRP-1 by activated Wnt/β-catenin signaling pathway.(3)Moderate intensity treadmill exercise can activate the Wnt/β-catenin signaling pathway... |
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