Persistence of Exercise Training Effect on Amyloid Pathology

Abstract

BackgroundEarly life aerobic exercise training (ET) reduces amyloid beta (Aβ) plaque load and improves cognition in transgenic mouse models of Alzheimer's Disease (Yuede, et al. Neurobiology of Disease, 35, 2009). Many people are physically active into early adulthood, but it is less likely that they continue lifelong ET. In addition, it is unclear if the benefits of early ET persist into later life. We examined the persistence of ET effects by measuring cognition and plaque load at 12 months of age in transgenic mice that had participated in ET during various periods of life.MethodsThree groups of male APP/PS1 mice ran on a motorized treadmill at 20 m/min five days a week for 12 weeks at different times during their first year of life; EARLY (from 3–6 months), MIDLIFE (from 6–9 months), and LATE (from 9–12 months of age). A fourth group did not exercise train and served as sedentary controls (SED). At 12 months of age, all groups underwent Novel Object Recognition (NOR) and Morris Water Maze (MWM) testing to assess recognition memory and spatial learning. Brain hemispheres were collected for Thioflavin S staining to assay plaque load and for protein quantification. Soleus muscles were assayed for citrate synthase activity to verify the effectiveness of the ET regimen.ResultsOne‐way ANOVA revealed a significant main effect of ET on citrate synthase activity with the LATE group having 25.8% greater activity. There was also a significant effect of ET on cognition though the effect was limited to the most recently trained groups and absent in the EARLY animals. There was a main effect of ET group on the latency to platform during the MWM Place Trials with significantly lower latencies in the MIDLIFE and LATE groups compared to SED and EARLY. Similarly, there was an increased time in target region in the LATE group compared to others in the MWM Probe trials. Recognition memory was also improved in the LATE group as demonstrated by a greater novel investigation time relative to the other groups. Finally, there was significantly lower plaque load in MIDLIFE and LATE animals (59.6% and 45.8% lower than SED, respectively).ConclusionThere are significant cognitive benefit of ET, but little persistence once ET is discontinued in APP/PS1 mice. Interestingly, LATE group data provide evidence that beginning ET later in the amyloidogenic process is still effective at preserving cognitive function and reducing plaque load. Protein analysis is on‐going and will assess the impact of ET on brain signaling and clearance proteins in these 4 groups.Support or Funding InformationSupported by Missouri State Research FundsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.