Overall, exercise can promote the expression of BDNF and CREB by increasing SIRT1 expression in the hippocampus, and moreover, it can activate the SIRT1/IGF-1/GAP-43 and SYN signaling pathways to increase the volume of SVZ and SGZ, improving neurogenesis, and eventually relieving depression (as shown in Figure 1). Here, CREB1 is linked to major depressive disorder.