Our data indicated a substantial increase in BDNF expression and enhanced ratios of phosphorylated TrkB (p-TrkB) to TrkB, as well as phosphorylated AKT (p-AKT) to AKT in both the hippocampus and cortex of mice afflicted with depression after treatment with RVG-BDNF-Exos (Fig. 4C to H). This evidence concerns the gene BDNF and major depressive disorder.