Influence of aerobic exercise on cognitive function in the TgF344-AD model of Alzheimer's disease

Introduction – Exercise therapy is a promising strategy for Alzheimer’s disease (AD) protection although our understanding of exercise-induced neuroprotection remains incomplete. The goal of the present study is to longitudinally characterize the influence of exercise training on changes in cognitive function in both male and female TgF344-AD rats. We hypothesize that cognitive function will be impaired by AD and exercise-training will rescue AD-induced impairments. Methods – Male and female TgF344-AD rats (n=62) began a six-month progressive treadmill training protocol at 12 months of age. Training was conducted 5 days per week and intensity maximized at 24 meters per minute for 60 minutes. Behavioral testing, including Morris Water Maze (spatial learning and memory), Rotarod (motor coordination), and grip strength (muscular strength), was conducted at months (m) 3, 6, 9, 12 (pre-intervention), and 13-18 (post-intervention). Investigators were blind to presence of AD. Differences were identified with Bayesian multivariate linear regression. Results – Memory (latency time, s) was rescued by exercise in female AD rats. Post-intervention, female exercise groups demonstrated improved memory (-0.02 log scale s/m) while sedentary controls declined; no exercise effect was detected in male wild-type (WT) or AD groups. Grip strength is represented relative to body weight (g/g). Post-intervention, average grip strength declined across all groups and declines were greater in AD compared to WT animals (-0.038 vs -0.011 log-transformed g/g per month). Exercise attenuated the age-related declines compared to sedentary controls (0.001 vs -0.0498).The rate of grip strength loss from 13 m to 18 m was one-eighth the rate in female AD exercisers compared to female AD sedentary (-0.009 vs -0.075) while male AD exercisers lost strength at one-fourth the rate compared to male AD sedentary (-0.013 vs -0.054). Conclusions – In the present study the influence of advanced age, AD genotype, and exercise training in the TgF344-AD rat manifested in a sex-specific manner. In females, exercise training ameliorated AD-induced memory deficits and ameliorated age- and AD-induced strength declines to a greater degree than males. Our time-wise characterization of memory and grip strength in the TgF344-AD rat provides valuable reference for future biochemical analysis aimed at elucidating mechanisms of exercise-induced neuroprotection. R03 AG065970, P20GM113109 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.