Voluntary exercise increases adult hippocampal neurogenesis by increasing GSK-3β activity in mice

Exercise has been proven to promote learning and memory, and is closely related to increased adult neurogenesis in the hippocampus. In our study, the β subunit of Glycogen synthase kinase-3 (GSK3β) can be significantly regulated by exercise, and the modulation of GSK3β activity can enhance adult neurogenesis and memory. To explore the mechanism by which exercise can improve cognitive function and adult neurogenesis, and the role GSK3β plays in this process, we established a mouse model of voluntary exercise to examine the expression and activity of GSK3β, and its associated signaling pathways, in the hippocampus dentate gyrus. The results showed an obvious increase in adult neurogenesis and cognitive functions, and the up-regulation of GSK3β, after exercise. The activity of the insulin pathway, which negatively regulates GSK3β, was also increased. Moreover, our results showed that the dopamine D₁ receptor (DARP D₁) pathway and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) were also activated, which indicates a relationship between GSK3β and neurogenesis. Overall, our findings demonstrated that voluntary exercise promotes cognition and neurogenesis in the adult mouse dentate gyrus by the regulation of GSK3β expression and activity, which may be implemented through the DARP D₁ receptor-signaling pathway.