〔Abstract〕 Objective To investigate the expression of prefrontal cortical neurons ，methyltransferase-like 3 （METTL3），fat mass and obesity-associated gene（FTO）， and AlkB homolog 5（ALKBH5）proteins in a mouse model of post-traumatic stress disorder（PTSD）. Methods A PTSD mouse model was established using a single prolonged stress and foot shock stimulation（SPS&S）method. The despair，anxiety，and learning and memory functions of PTSD mice were assessed through the open field test，Y-maze test，and forced swimming test. Neuro_ nal damage was detected via HE and Nissl staining. The expression levels of METTL3，FTO，ALKBH5，and neu_ ronal nuclear protein（NEUN）were assessed by Western blot and immunofluorescence staining. Results Com_ pared to control group，PTSD mice subjected to SPS&S exhibited signs of despair，anxiety，and impaired learning and memory. HE and Nissl staining results showed neuronal damage in the prefrontal cortex of PTSD mice. West_ ern blot and immunofluorescence staining results showed that the expression of the m6A-related proteins METTL3 and FTO decreased，while the expression of ALKBH5 increased in the prefrontal cortex. Additionally，NEUN pro_ tein levels showed a declining trend. Conclusion The pathogenesis of PTSD may be associated with neuronal dam_ age in the prefrontal cortex and alterations in m6A methylation proteins.