Abstract

Posttraumatic stress disorder (PTSD) is a serious stress disorder that occurs in individuals who have experienced major traumatic events. The underlying pathological mechanisms of PTSD are complex, and the related predisposing factors are still not fully understood. In this study, label-free quantitative proteomics and untargeted metabolomics were used to comprehensively characterize changes in a PTSD mice model. Differential expression analysis showed that 12 metabolites and 27 proteins were significantly differentially expressed between the two groups. Bioinformatics analysis revealed that the differentiated proteins were mostly enriched in: small molecule binding, transporter activity, extracellular region, extracellular space, endopeptidase activity, zymogen activation, hydrolase activity, proteolysis, peptidase activity, sodium channel regulator activity. The differentially expressed metabolites were mainly enriched in Pyrimidine metabolism, D-Glutamine and D-glutamate metabolism, Alanine, aspartate and glutamate metabolism, Arginine biosynthesis, Glutathione metabolism, Arginine, and proline metabolism. These results expand the existing understanding of the molecular basis of the pathogenesis and progression of PTSD, and also suggest a new direction for potential therapeutic targets of PTSD. Therefore, the combination of urine proteomics and metabolomics explores a new approach for the study of the underlying pathological mechanisms of PTSD.

Highlights

  • Post-Traumatic Stress Disorder (PTSD) is a persistent stress disorder type that may be delayed or imminent following major psychological trauma (Kessler et al, 1995; Breslau et al, 1998)

  • There was no significant difference in terms of total arms entries (Figure 2A) and total time spent in the arms (Figure 2B) between the control and the Posttraumatic stress disorder (PTSD) groups

  • The induction of the electric foot shock stress caused a significant reduction in the percent of open arm entries with the ones of the control and the PTSD group being 45.4 and 27.5%, respectively (Figure 2C)

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Summary

Introduction

Post-Traumatic Stress Disorder (PTSD) is a persistent stress disorder type that may be delayed or imminent following major psychological trauma (Kessler et al, 1995; Breslau et al, 1998). PTSD has four core symptoms according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); the re-experiencing of traumatic event(s), continuous avoidance of trauma-related stimuli, negative emotions related to cognitive trauma, and continued increase in alertness (Mahan and Ressler, 2012; Tandon, 2014; Tanaka et al, 2019). Several of these aspects can be captured using situational reminder programming in animal models, leading it to become a common model for studying the PTSD Metabolomics and Proteomics Analysis symptoms and mechanisms of PTSD. Recent reports have shown that urine can provide a lot of non-urogenital information, including regarding neuropsychiatric disorders (Emanuele et al, 2010; Marc et al, 2011)

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