BDNF and CREB/BDNF signaling pathways, including the expression of BDNF, phospho-cAMP response element-binding protein (CREB) (pCREB), phospho-ERK1/2, phospho-Protein kinase B (AKT), and TrkB (a receptor of BDNF), were downregulated in the cerebral hippocampus of depression models that underwent stress (13, 14). This evidence concerns the gene BDNF and major depressive disorder.