Role of apoptosis in the Post-traumatic stress disorder model-single prolonged stressed rats

Post-traumatic stress disorder (PTSD) is a stress-related mental disorder which occurs following exposure to traumatic events. A number of brain neuroimaging studies have revealed that PTSD patients have reduced volume and abnormal functions in the hippocampus and the amygdala. However, the pathogenesis of abnormalities in certain brain regions, as induced by PTSD, remains unclear. Recent studies, using the single prolonged stress (SPS) model, an animal model of PTSD, have found that abnormal apoptosis in certain brain regions, including the hippocampus, the amygdala, and the medial prefrontal cortex (mPFC); these areas are closely associated with emotion and cognition. In this review, we summarize the mechanism of apoptosis in SPS rats, including the endoplasmic reticulum (ER) and the mitochondria pathways. For the ER pathway, three individual pathways: PERK, IRE1, and ATF6 showed different roles on apoptosis and neuroprotection. Three key factors are thought to be involved in the mitochondrial pathway and PTSD-induced apoptosis: corticosteroid receptors, apoptosis-related factors, and anti-apoptosis factors. We have investigated the role of these factors and have attempted to identify which factors of the pathways are more focused towards neuronal protection, and which are more direct towards apoptosis. We also discussed the role of autophagy and the specific differences between autophagy and apoptosis in SPS rats. Finally, we discussed emerging researches related to anti-apoptosis treatment, including PERK inhibitors, IRE1 inhibitors, and metformin; collectively, these were exciting, but limited, This review provides a summary of the current understanding of apoptosis in SPS rats and the potential anti-apoptosis treatment strategies for PTSD.