Effects of Different Exercise Strategies and Intensities on Memory Performance and Neurogenesis

Abstract

It is well established that physical exercise affects both hippocampal neurogenesis and memory functions. Until now, distinctive effects of controlled and voluntary training (VT) on behavior and neurogenesis as well as interactions between exercise intensity, neurogenesis and memory performance are still elusive. The present study tested the impact of moderate controlled and VT on memory formation and hippocampal neurogenesis and evaluated interactions between exercise performance, learning efficiency and proliferation of progenitor cells in the hippocampus. Our data show that both controlled and VT augmented spatial learning and promoted hippocampal neurogenesis. Regression analysis revealed a significant linear increase of the amount of new hippocampal neurons with increased exercise intensity. Regression analysis of exercise performance on retention memory performance revealed a quadratic, inverted u-shaped relationship between exercise performance and retention of spatial memory. No association was found between the amount of newborn neurons and memory performance. Our results demonstrate that controlled training (CT), if performed with an appropriate combination of speed and duration, improves memory performance and neurogenesis. Voluntary exercise elevates neurogenesis dose dependently to high levels. Best cognitive improvement was achieved with moderate exercise performance.

Keywords: exercise; hippocampal neurogenesis; learning and memory.

Figure 1

Experimental design.

Figure 2

Effects of physical exercise on spatial learning and memory formation in the Morris water maze task. (A) Both controlled (CT) and voluntary training (VT) improved acquisition of spatial memory compared to sedentary control (SED) (SED vs. VT p = 0.023, SED vs. CT p = 0.029, Fisher’s least significant difference (LSD) test after significant ANOVA). (B) Analyses of the amount of crossings over the former platform area revealed a significant group effect (p < 0.001, ANOVA) and a significant effect of CT vs. SED (***p < 0.001, Fisher’s LSD test), no significant difference between VT vs. SED (p = 0.179, Fisher’s LSD test) and a significant difference between CT and VT (**p = 0.002, Fisher’s LSD test). (C) Analysis of the time spent in the maze quadrants showed that mice of all groups spend significantly more time in the target quadrant (Q2) than any of the other quadrants (SED: p = 0.041, VT: p < 0.001, CT: p < 0.001; one-way ANOVA). The target quadrant occupancy of trained mice was significantly higher when compared with SED mice (SED vs. VT: p = 0.02, SED vs. CT: p = 0.001, Fisher’s LSD test after significant ANOVA, *p < 0.05, **p < 0.01).

Figure 3

Quantification of neurogenesis by the detection of BrdU/NeuN-expressing cells. (A,B) Analysis of the number of BrdU and BrdU/NeuN positive cells revealed increased amounts of newborn cells in the dentate gyrus following CT and VT compared to the SED group (p < 0.001, ANOVA; *p < 0.05, **p < 0.01, ***p < 0.001; Fisher’s LSD test). The most prominent difference in the amount of newborn neurons was found between the CT and SED group (p < 0.001, Fisher’s LSD test). There was a discernible albeit insignificant difference between CT and VT group (p = 0.084, Fisher’s LSD test). (C) Photomicrographs showing representative images of bromodeoxyuridine (BrdU, red) and NeuN (green) staining in the dentate gyrus of animals of the SED, the VT and the CT group. Scale bar corresponds to 100 μm.

Figure 4

Regression analyses of exercise performance on neurogenesis and memory retention. (A) Analyses revealed a linear relationship between the total running distance and the amount of newborn neurons (p < 0.0001, β = 0.913). (B,C) Regression analyses of exercise performance on retention memory showed a quadratic, inverted u-shaped relationship for the amount of platform crossings (exercise performance: β = 2.194, p = 0.006; exercise performance²: β = −2.209, p = 0.006) and time spent in the correct quadrant (exercise performance: β = 1.659, p = 0.045; exercise performance²: β = −1.801, p = 0.031).