E-36 Free Communication/Poster - Neuroscience Friday, May 30, 2014, 7:30 AM - 12:30 PM Room:WB1
PURPOSE: To investigate the effect of treadmill running on cognitive impairments and pathologic hallmarks of Alzheimer’s disease using a triple-transgenic mouse model of Alzheimer’s disease (3xTg-AD).
METHODS: At 24-mo postnatal period, 3xTg-AD mice (N=16) were assigned to sedentary (AD+SED, n=8) or exercise group (AD+EXE, n=8). AD+EXE mice were subjected to running on a motor-driven animal treadmill for 12 weeks (10 m/min, 30 min/session, 5 days/week), while AD+SED mice remained sedentary. Morris water maze (MWM) test was performed for cognitive function after the 12-week treatments. Immunostaing and western blotting were used to quantify several of the pathologic hallmarks of the disease.
RESULTS: After the 12-week treatments, the AD+EXE mice had shorter escape latencies (41.9±3.1 vs. 54.8±2.3s, p=0.02) and greater short- (24.0±10.4 vs. 13.6±5.2s, p=0.001) and long-term memory retentions (16.0±2.5 vs. 11.6±3.6s, p=0.02) on the MWM tests than the AD+SED mice. With respect to AD pathology, the AD+EXE mice had significantly lower levels of soluble Aβ 1-40 (5.2±0.1 vs. 6.4±0.09pg/μg, p=001), soluble Aβ 1-42 (15.4±0.05 vs. 16.7±0.5pg/μg, p=0.04), beta-site amyloid protein precursor (APP)-cleaving enzyme1 (0.5±0.09 vs. 1.1±0.02, p=0.03) and β-secretase cleaved APP-c-terminal fragment (3.5±0.1 vs. 7.2±0.4, p=0.001) but higher levels of postsynaptic density protein-95 (0.58±0.08 vs. 0.24±0.03, p=0.001), synaptophysin (0.91±0.01 vs. 0.32±0.07, p=0.02) and brain-derived neurotrophic factor (0.98±0.1 vs. 0.46±0.08, p=0.001) in the hippocampus and cerebral cortex than the AD+SED mice.
CONCLUSION: The findings of the study suggest that 1) exercise training suppresses cognitive deficits of AD and 2) suppression of APP-processing enzymes and enhanced synaptic stability in the hippocampus and cerebral cortex are involved in exercise training-induced suppression of AD-like cognitive deficits.
(This study was supported by the Korean Government Research Foundation funded by the Korean Government (NRF-2012R1A1A2006180) (NRF-2013S1A5B5A01029303)).