Enhancement of neurogenesis by running wheel exercises is suppressed in mice lacking NMDA receptor ε1 subunit

Neurogenesis continues throughout adulthood in the dentate gyrus in mice, and is regulated by environmental, endocrine, and pharmacological stimuli. Although running wheel exercises have been reported to enhance neurogenesis, details of molecule mechanisms of the enhancement are not well understood. We report here that the hippocampal neurogenesis is enhanced when wild-type mice are raised in cages with running wheels for 3 weeks, but the wheel exercise does not enhance the neurogenesis in mice lacking the NMDA receptor ε1 subunit. Brain-derived neurotrophic factor (BDNF) has been reported to affect neuronal cell proliferation and survival. We examined the BDNF levels in the hippocampi of wild-type and ε1 knockout mice, and found that the BDNF level was increased through wheel exercises in the wild-type but not in the knockout mice. The enhancement of neurogenesis by the wheel exercise was also found to be reversible: when the exercise-stimulated wild-type mice were returned to the environment without running wheels for 3 weeks, the neurogenesis was the same as that in the mice which had never experienced the exercise. These results suggest that the wheel exercise may activate NMDA receptors in the hippocampus, which in turn may enhance BDNF production and neurogenesis.