Exercise and time-dependent benefits to learning and memory

Abstract

While it is well established that exercise can improve cognitive performance, it is unclear how long these benefits endure after exercise has ended. Accordingly, the effects of voluntary exercise on cognitive function and brain-derived neurotrophic factor (BDNF) protein levels, a major player in the mechanisms governing the dynamics of memory formation and storage, were assessed immediately after a 3-week running period, or after a 1-week or 2-week delay following the exercise period. All exercised mice showed improved performance on the radial arm water maze relative to sedentary animals. Unexpectedly, fastest acquisition (fewest errors and shortest latency) occurred in animals trained following a 1-week delay, while best memory performance in the probe trial was observed in those trained immediately after the exercise period. Assessment of the time course of hippocampal BDNF availability following exercise revealed significant elevations of BDNF immediately after the exercise period (186% of sedentary levels) and at 1 and 2 weeks after exercise ended, with levels returning to baseline by 3-4 weeks. BDNF protein levels showed a positive correlation with cognitive improvement in radial water maze training and with memory performance on day 4, supporting the idea that BDNF availability contributes to the time-dependent cognitive benefits of exercise revealed in this study. Overall, this novel approach assessing the temporal endurance of cognitive and biochemical effects of exercise unveils new concepts in the exercise-learning field, and reveals that beneficial effects of exercise on brain plasticity continue to evolve even after exercise has ended.

Figure 1

Exercise effects on acquisition and retention of the radial water maze. Latency and errors by day (A,D) or by blocks of 5 trials (B,C, E, F) after 3 weeks of voluntary wheel running exercise with no delay (EX), a 1-week delay (EX/delay-1) or a 2-week delay (EX/delay-2) between exercise and cognitive training. Latency or errors by day (averaged over 2 blocks of 5 trials per day) reveals that animals with exercise exposure learn the task faster than sedentary animals (A, D). Latency and errors by block of 5 trials (B,E) reveals that EX and SED groups have similar latencies to find the platform (B) while the EX group ultimately makes fewer errors on block 6 (E). Latency and errors by block of 5 trials (C, F) reveals that fastest acquisition was observed when a 1-week delay was introduced between exercise and cognitive training while after 2 weeks delay, acquisition speed was intermediate between the performance of SED and EX/Delay-1 groups. Failure to find the escape platform was more frequent in SED than EX animals in block 1 of training (G). Probe trial performance reveals that all animals learned the task, spending more time in the target arm where the platform had been located, relative to the other maze arms (H). Exercised animals showed greater preference for the target arm relative to SED animals, with strongest memory in animals with no delay between exercise and cognitive training. Percentage of time in each arm was calculated as the ratio of “time in arm” divided by “time spent in all arms”. All data are averages ± sem. (SED vs EX: ^δ p ≤ 0.05, ^δδ p ≤ 0.01. SED vs EX/Delay-1: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.005. SED vs EX/Delay-2: ^σ p ≤ 0.05. EX vs EX/Delay-1: ^Ψp ≤ 0.05, ^ΨΨp ≤ 0.01. EX/Delay-1 vs EX/Delay-2: ^χp ≤ 0.05. Target arm vs non-target arms: ^ϕϕ p ≤ 0.0001)).

Figure 2

BDNF protein levels are elevated after 3 weeks of exercise, progressively decline after exercise ends, and correlate with performance in the radial water maze. While reduced from peak levels at the end of exercise, BDNF protein levels remain elevated over sedentary levels for several weeks after exercise has ended (A). Regression analysis reveals that higher BDNF protein levels correlate with better “improvement scores” (errors_{(block 1)} – errors_{(block 6)}) (B) and with longer time searching in the target arm in the memory probe trial on day 4 (C). Log curves were fitted to the regression data. Values shown are averages ± sem (significance vs SED: * p≤0.05, *** p≤0.0001, ^# p=0.075).