A substantial amount of evidence has shown that treadmill running enhances neurogenesis, improves cognitive function, and protects the brain against neurodegenerative disorders. However, treadmill running is a type of forced exercise that could increase the level of corticosterone, which subsequently down-regulates neurogenesis and impairs cognitive function. The purpose of this study was to investigate if regular treadmill running provides a balance between the positive and negative effects of treadmill running. The mice were divided into four groups: controls (CON), regular runners (RR), irregular duration runners (IDR) and irregular time-of-day runners (ITR). The RR mice ran daily on the treadmill at the same time-of-day, speed and duration. The IDR mice ran at the same time-of-day and speed, but for a different duration. The ITR mice ran at the same speed and duration, but at different time-of-day. The results showed that regular treadmill running could increase neurogenesis and improve spatial learning and memory performance, as well as decrease the level of corticosterone. The present finding emphasizes the importance of regular physical exercise on cognition.

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