Research on Effect ofα-secretase on Regulating Hippocampal APP and Aβ42 in APP/PS1 Transgenic Mice of Alzheimer’s disease after Voluntary Wheel Running

Objective:To observe the effect ofα-secretase on the hippocampal APP cleaving and Aβ42deposition in transgenic mice of Alzheimer's disease(AD)after 16 weeks voluntary wheel running.Methods:24 male APP/PS1 transgenic mice of line C57 that expresses human mutant APP and PS1 in the brain were chosen and divided into wheel running group(TE,n=12)and control group(TC,n=12).Meanwhile,24 male wild-type mice in line C57 were chose and divided into wheel running group(E,n=12)and control group(C,n=12).Mice in group TE and group E were subjected to wheel running with ad libitum access to food and water for 16 weeks from 3 months of age.Mice in group TC and group C were subjected to food and water ad libitum,without exercise.Real-time RT-PCR was used to detect mRNA level of the main member ofα-secretase,ADAM9,ADAM10 and ADAM17.Western blot was used to detect protein level of APP,ADAM10 and Aβ42.Results:(1)16weeks wheel running significantly up-regulated the expression of ADAM10 mRNA(P<0.01)and ADAM10protein(P<0.05)in the hippocampus of APP/PS1 transgenic mice.(2)16weeks wheel running significantly up-regulated the expression of ADAM17 mRNA(P<0.05)in the hippocampus of APP/PS1 transgenic mice.(3)16 weeks wheel running significantly decreased the protein expression of APP(P<0.05)and Aβ42(P<0.05)in the hippocampus of APP/PS1 transgenic mice.Conclusion:16weeks wheel running decreased the level of APP and its production Aβ42by promoting the gene expression ofα-secretase in the hippocampus of APP/PS1 transgenic mice.