Research On The New PTSD Mouse Model And The Glucocorticoid Effect In PTSD

Objective:The purpose of this study is to evaluate a novel mouse model of post-traumatic stress disorder and to investigate the effect of early intervention with the selective serotonin reuptake inhibitor (paroxetine), corticosterone and glucocorticoid receptor antagonist (RU38486) in this PTSD model.Methods:Male KM mice suffered double stresses-conditional fear (CF) and single-prolonged stress (SPS). After latency period, the behavioral changes of mice were observed with the conditioned fear test (CF), open field (OF) test, elevated plus maze (EMP) test, spontaneous activity test (SLT) and novel object recognition task (NOR). The apoptosis of hippocampus cells in PTSD mice was determined by flow cytometry experiments (FCM) and terminal transferase dUTP nick-end labeling (TUNEL) experiments. And the morphologic changes of neuronal and synaptic ultrastructures of hippocampus were analyzed by transmission electron microscopy examinations (TEM).Furthermore, we studied the preventive effects of early intervention with the selective serotonin reuptake inhibitor (paroxetine, PRX), corticosterone (CORT) and glucocorticoid receptor antagonist (RU38486) in this PTSD model.Results:After latency period, the mice exhibited low activities and disliked entering into the center of the open field and the open arms. The mice also exhibited defects in novel object recognition abilities. The flow cytometry experiments showed that the apoptosis rates in hippocampal neurons were increased in this double stresses model. The expressions of c-fos and Bax protein in the Western Blotting experiments were increased significantly in hippocampus; conversely, the Bcl-2, synapsin and synaptotagmin protein expressions were decreased. Electron microscopy analysis of neuron and synaptic ultrastructure further noted the synaptic losses and neuronal impairments in hippocampus of the model mice.The preventive effects of early intervention with PRX, CORT and RU38486 results showed that PRX, CORT and RU38486 reduced PTSD-like behaviors and inhibited the apoptotic changes in the hippocampal region.Conclusions:This mouse model is novel and more predictably mimicked the clinical characteristics of PTSD. This model can be further used for investigating the mechanisms of PTSD and screening effective therapeutics agents. Early intervention with RU38486 was an effective way to reduce the incidence of PTSD symptoms.