The impact of chronic stress on the PFC transcriptome: a bioinformatic meta-analysis of publicly available RNA-sequencing datasets

The prefrontal cortex (PFC) is one of several brain structures that are sensitive to chronic stress exposure. There have been several studies which have examined the effects on chronic stress, using various protocols such as chronic unpredictable stress and chronic social defeat stress, on the PFC transcriptome. In this report, a bioinformatic meta-analysis of publicly available RNA sequencing datasets (101 samples) from seven chronic stress studies was carried out to identify core PFC transcriptional signatures that underpin behavioral phenotypes including resilience and susceptibility. The results showed 160 differentially expressed genes in chronic stress mice compared to controls with significant enrichment in mechanisms associated with translation and localization of membrane-bound proteins with a putative effect on synaptic plasticity in glutamatergic neurons. Moreover, the meta-analysis revealed no differentially expressed genes in resilient mice but 144 in susceptible mice compared to controls, of which 44 were not identified in the individual studies. Enrichment analysis revealed that susceptibility genes were most affected in oligodendrocytes and linked to mechanisms which mediate biochemical, bidirectional communication between this cell-type and myelinated axons. These results provide new avenues for further research into the neurobiology and treatment of chronic stress-induced disorders.