Metabolomic analysis and signatures in mouse model of post traumatic stress disorder

We have used a social defeat (SD) mouse model of post‐traumatic stress disorder (PTSD) that is based on a brief exposure of a mouse to the aggressor mice in order to investigate the influence of chronic (5–10 day) predator/aggressor exposure and determine the progression that occurs upon “recovery” 4–6 weeks later. Mice simulating aspects of posttraumatic stress disorder exhibit abnormalities in many behavioral tendencies such as frozen motion, aggressor barrier avoidance, startled jumping when in contact with aggressor, decreased‐object recognition and tail suspension immobility. This disease model has produced characteristic perturbations of the metabolome, and will enable simultaneous quantification of a large number of metabolites to identify metabolic signatures as biomarkers for disease. Biomarkers that are specific and sensitive to PTSD would facilitate early diagnosis, disease progression monitoring and drug development. In this study, we take a targeted electrochemistry based approach for the comprehensive identification of the metabolites. Global metabolic profiling was carried out on plasma from terminal bleeds of mice exposed to either 5 day or 10 day of SD at both early (24h) and late (1.5 weeks for the 5d SD and 4 weeks for the 10d SD) time points. This approach permitted the detection of 496 small molecules among the four groups tested. Of these 330 were known compounds and 166 were unknowns. We observed alterations in neurotransmitters and neurotransmitter –related biochemicals. Data also suggested that there were redox changes, neuronal damage and/or cell death and energetic alterations. The majority of the significant alterations occurred in the early 24h time point following 5days of SD. Results from this study may help to facilitate identification of new avenues worthy for investigation for prevention, diagnosis and treatment of PTSD.