BDNF and major depressive disorder: 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).