Cell type specificity of glucocorticoid signaling in the adult mouse hippocampus

Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1) and the mineralocorticoid receptor (MR: Nr3c2). These nuclear steroid receptors act as ligand-dependent transcription factors. Transcriptional effects of glucocorticoids have often been deduced from bulk mRNA measurements or spatially informed individual gene expression. However, only sparse data exists allowing insights on glucocorticoid-driven gene transcription at the cell type level. Here, we used publicly available single-cell RNA sequencing data to assess the cell-type specificity of GR and MR signaling in the adult mouse hippocampus. The data confirmed that Nr3c1 and Nr3c2 expression differs across neuronal and non-neuronal cell populations. We analyzed co-expression with sex hormones receptors, transcriptional coregulators, and receptors for neurotransmitters and neuropeptides. Our results provide insights in the cellular basis of previous bulk mRNA results and allow the formulation of more defined hypotheses on the effects of glucocorticoids on hippocampal function.

Automated summary

Glucocorticoid stress hormones can affect mood and cognitive processes in the brain, with the hippocampus being a prominent target expressing GR and MR receptors. Analysis of single-cell RNA sequencing data confirmed cell-type specificity of GR and MR signaling, providing insights into cellular basis of glucocorticoid effects on hippocampal function.