Effect of corticosterone on the gene expression in the context of global hippocampal transcription

The composition of genomic mediators of glucocorticoids in brain remains elusive because of common problem of low statistical power of experiments and associated very low consistency of transcriptomic data. Other issues is underrepresentation of chronic experiments and interpretation of differentially expressed genes without understanding their contribution to the total transcriptomic activity. To fill existing gaps in knowledge we have performed a large transcriptomic experiment (48 mice in total) testing effects of prolonged treatment with corticosterone (5, 14 and 28 days) on hippocampal transcriptome (RNA sequencing) and, next, we have assessed the contribution of differentially expressed genes to total transcriptomic activity. The experiment showed that prolonged treatment with the corticosterone induced a set of transcriptomic effects that were replicable across treatment durations including genes relevant for human PTSD (Opalin, Pllp, Ttyh2, Lpar1) and prolonged stress in animals (Cnp, Fam163a, Fcrls, Tmem125). Part of affected genes is specific for oligodendrocytes, neurons, astrocytes, immune cells, vascular system and brain ventricles indicating that glucocorticoids may affect all components of the central nervous system. The data showed also that the largest changes in expression of corticosterone-responsive genes are restricted to genes that have relatively low expression level and small contribution to the overall pool of mRNAs in the hippocampus. As a result, even large change in terms of the number of affected genes leads to small change in the number of mRNA copies. This means, in turn, that the transcriptomic changes induced by corticosterone are a low-cost effects for the brain.