The results indicated that PTBP1 KD ameliorates PTSD-like behaviors in mice by balancing Bcl-2/Bax expression and suppressing Caspase-3 splicing activation to inhibit hippocampal neuronal apoptosis, enhancing synaptic plasticity through upregulating PSD95 and SYN1, increasing dendritic spine density and stabilizing axonal architecture via elevated NF200 expression. Here, CASP3 is linked to post-traumatic stress disorder.