HES5 and major depressive disorder: For example, Guo et al. observed the Notch signaling pathway in the hippocampus of post-stroke depression rats and found that the Notch signaling pathway in the hippocampus of depression rats is inhibited, neuronal apoptosis and necrosis are increased, and there are few newborn neurons; after intervention with antidepressants, the Notch signaling pathway was activated, and the protein expression of key targets (especially Hes1 and Hes5) increased, which promoted the increase of newborn neurons and alleviated depressive behavior (Guo et al., 2009).