Further investigation of the PI3K/AKT pathway’s upstream (BDNF, TrkB) and downstream (CREB) depression-related proteins demonstrated that CUMS induction significantly reduced hippocampal levels of BDNF, TrkB, and p-CREB/CREB (Figures 6A–C), as detected by WB. The gene discussed is CREB1; the disease is major depressive disorder.