Exercise Training Protects Against Aging-Induced Cognitive Dysfunction via Activation of the Hippocampal PGC-1α/FNDC5/BDNF Pathway

This study aimed to determine the effect of exercise training on cognitive functioning, and hippocampal PGC-1α, FNDC5, BDNF, and other cognition-related gene and protein expression in rats. Rats were divided into 4 groups based on age [3 months (young) vs. 20 months (aged)] and training status (control vs. exercise training). The rats that exercised voluntarily performed exercise training for 90 days, and then all the rats underwent several methods of behavioral assessment. Locomotor activity and spatial memory were lower but anxiety scores were higher in the aged control rats, than in the young control, young exercised, and aged exercised rats (P < 0.05). Hippocampal BDNF, FNDC5, PGC-1α, mTOR, ARC, cF-OS, ERK, SIRT, and FOXO expressions were lower, but NF-κB expressions were higher in the aged control rats than in the young control, young exercised, and aged exercised rats (P < 0.05). Similarly, hippocampal BDNF and FNDC5 protein expression were lower in the aged control rats than in the young control, young exercised, and aged exercised rats (P < 0.05). These findings show that aging-induced cognitive dysfunction is associated with a decrease in hippocampal expression of PGC-1α, FNDC5, and BDNF, and that exercise training might improve cognitive functioning via activation of these genes and proteins.