Aerobic Exercise Attenuates The Aβ Oligomer-induced Mitochondrial Permeability Transition Pore Opening In App/ps1 Transgenic Mice

Abstract

PURPOSE: The mitochondrial permeability transition pore (mPTP) plays a role in the onset and the progression of Alzheimer’s disease (AD). This study was to analyze the effects of 12 weeks aerobic exercises on mPTP activation in AD models mice. METHODS: 6-month-old of APP/PS1 transgenic mice and C57BL/6J mice were randomly divided into exercise group (CE, AE) and sedentary group (AS, CS) respectively. The exercised mice were subjected to a treadmill exercise for 12 weeks, then the experimental age was at 9-month-old. The behavioral changes were detected by eight arm maze. Immunofluorescence, histochemistry and Dot blot were to analyze mPTP opening, the level of amyloid-β (Aβ) and soluble oligomers (oAβ). ELISA and Western Blotting were used to detect the activity of COXIV, ABAD, and the levels of COXIV, ABAD, Cyp-D, ANT1, ANT2, VDAC-1. RESULTS: Bothworking memory errors and reference memory errors were significantly increased in AS compared with those in the CS (40±4 vs.30±4%; 71±2 vs.54±1%, p<0.01). The AE performed better than AS (22±1 vs.39±3%; 55±3 vs.71±2%, p<0.05). Aβ was aggregated at hippocampus in AS, accompanied with an increase of oAβ (1vs.1.1±0.1, p<0.05). A decline was detected in Aβ plaque and oAβ content in AE than AS (0.6±0.1vs.1.5±0.1; 0.9±0.1 vs.1.1±0.1, p<0.05). There was an increase in AS compared with CS in the mPTP opening (0.07±0.002vs.0.08±0.002, p<0.01), and which was decreased after aerobic exercise (0.07±0.002vs.0.08±0.003, p<0.01). AS displayed an increase in Cyp-D, ANT1, VDAC-1, ABAD of the hippocampus compared with the CS (1.1±0.1vs.1, p<0.05), but a decrease in ANT2, COXIV protein (0.9±0.1vs.1, p<0.01). Aerobic exercise decreased the expression of Cyp-D, ANT1, VDAC-1, ABAD in AS (1.1±0.1vs.1±0.1, p<0.05) and increased ANT2, COXIV (0.9±0.1vs.1±0.1, p<0.05). The activity of COXIV and ABAD in the hippocampus of AS were decreased compared with those of the CS (3.3±0.1vs.3.7±0.2; 0.5±0.1vs.1±0.2, p<0.01), and aerobic exercise caused an increase of their activities (3.3±0.1vs.5.6±0.2; 0.5±0.1vs.0.8±0.1, p<0.01). CONCLUSIONS: Aerobic exercise attenuates the oAβ deposition and the opening of mPTP, then regulates the mitochondrial oxidative phosphorylation for energy production in AD models. Supported by the National Natural Science Foundation of China (NSFC) (No. 31571229)