Identification of Critical Signature in Posttraumatic Stress Disorder Using Bioinformatics Analysis and Vitro Analyses

Background : Post-traumatic stress disorder (PTSD) is a complicated psychiatric disorder after experiencing trauma that affects people’s natural lives. As such, the objective of the study was mining related pathways and key genes of PTSD validated through vitro experiments. Method : Retrieving RNA sequencing (RNA-seq) datasets from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened using GEO2R. KEGG pathway assessment was carried out for enrichment analysis. The plugin MCODE from Cytoscape software was utilized to analyze the protein-protein interaction (PPI) network. Assessment of anxiety and depression in a mice model of stress was carried out by the open-field test (OFT) and elevated plus maze test (EPMT). Subsequently, Real-Time quantitative PCR (qRT-PCR) was used to verify these key genes in stress-exposed models. Results: A total of 157 common upregulated DEGs and 53 common downregulated DEGs were identified between the amygdala (AMY) and the hippocampus (HIP). Notably enriched pathways (Neuroactive ligand-receptor interaction, mTOR signaling pathway, Nicotine addiction and dopaminergic synapse, etc.) were screened by Gene functional annotations and enrichment analysis. The PPI network identified the 4 hub genes , finding that the closely related pathways were Nicotine addiction and dopaminergic synapse. qRT-PCR was used to confirm these four genes and the expressing trends were consistent with the microarray analysis. The results of the OFT and the EMPT were remarkable changes. Conclusion: Using bioinformatic analysis and in vitro experiments, we explored a variety of genes and pathways that may represent key mechanisms in the development of PTSD.