Treadmill Exercise Improves Memory Function Depending on Circadian Rhythm Changes in Mice

PURPOSE Exercise enhances memory function by increasing neurogenesis in the hippocampus, and circadian rhythms modulate synaptic plasticity in the hippocampus. The circadian rhythm-dependent effects of treadmill exercise on memory function in relation with neurogenesis were investigated using mice. METHODS The step-down avoidance test was used to evaluate short-term memory, the 8-arm maze test was used to test spatial learning ability, and 5-bromo-2'-deoxyuridine immunofluorescence was used to assess neurogenesis. Western blotting was also performed to assess levels of synaptic plasticity-associated proteins, such as brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element-binding protein, early growth response protein 1, postsynaptic density protein 95, and growth-associated protein 43. The mice in the treadmill exercise at zeitgeber 1 group started exercising 1 hour after sunrise, the mice in the treadmill exercise at zeitgeber 6 group started exercising 6 hours after sunrise, and the mice in the treadmill exercise at zeitgeber 13 group started exercising 1 hour after sunset. The mice in the exercise groups were forced to run on a motorized treadmill for 30 minutes once a day for 7 weeks. RESULTS Treadmill exercise improved short-term memory and spatial learning ability, and increased hippocampal neurogenesis and the expression of synaptic plasticity-associated proteins. These effects of treadmill exercise were stronger in mice that exercised during the day or in the evening than in mice that exercised at dawn. CONCLUSIONS Treadmill exercise improved memory function by increasing neurogenesis and the expression of synaptic plasticity-associated proteins. These results suggest that the memory-enhancing effect of treadmill exercise may depend on circadian rhythm changes.