The impact of psychosocial defeat stress on the bed nucleus of the stria terminalis transcriptome in adult male mice

The bed nucleus of the stria terminalis (BNST) is a focal point for the convergence of inputs from canonical stress-sensitive structures to fine-tune the response to stress. However, its role in mediating phenotypes of stress resilience or susceptibility is yet to be fully defined. In this study, we carried out unbiased RNA-sequencing to analyse the BNST transcriptomes of adult male mice, which were classified as resilient or susceptible following a 10-day chronic psychosocial defeat stress paradigm. Pairwise comparisons revealed 20 differentially expressed genes in resilience (6) and susceptible (14) mice compared with controls. An in silico validation of our data against an earlier study revealed significant concordance in gene expression profiles associated with resilience to chronic stress. Enrichment analysis revealed that resilience is linked to functions including retinoic acid hydrolase activity, phospholipase inhibitor and tumour necrosis factor (TNF)-receptor activities, whereas susceptibility is linked to alterations in amino acid transporter activity. We also identified differential usage of 134 exons across 103 genes associated with resilience and susceptibility; enrichment analysis for genes with differential exon usage in resilient mice was linked to functions including adrenergic receptor binding mice and oxysterol binding in susceptible mice. Our findings highlight the important and underappreciated role of the BNST in stress resilience and susceptibility and reveal research avenues for follow-up investigations.