As Sema3A is an axon guidance molecule (Perez et al., 2021) and the accumulation of Sema3A in the hippocampus can induce programmed cell death of neurons (Good et al., 2004), we speculate that the upregulation of hippocampal Sema3A in PPD mice influences synaptic plasticity or neuronal activity to cause anxiety and depression-like behaviors. Here, SEMA3A is linked to major depressive disorder.