Mineralocorticoid receptor status in the human brain after dexamethasone treatment: a single case study

BackgroundSynthetic glucocorticoids like dexamethasone can cause severe neuropsychiatric effects. They preferentially bind to the glucocorticoid receptor (GR) over the mineralocorticoid receptor (MR). High dosages result in strong GR activation but likely also result in lower MR activation based on GR-mediated negative feedback on cortisol levels. Therefore, reduced MR activity may contribute to dexamethasone-induced neuropsychiatric symptoms. ObjectiveIn this single case study, we evaluate whether dexamethasone leads to reduced MR activation in the human brain. Brain tissue of an 8-year-old brain tumor patient was used, who suffered chronically from dexamethasone-induced neuropsychiatric symptoms and deceased only hours after a high dose of dexamethasone. Main outcome measuresThe efficacy of dexamethasone to induce MR activity was determined in HEK293T cells using a reporter construct. Subcellular localization of GR and MR was assessed in paraffin-embedded hippocampal tissue from the patient and two controls. In hippocampal tissue from the patient and eight controls, mRNA of MR/GR target genes was measured. ResultsIn vitro, dexamethasone stimulated MR with low efficacy and low potency. Immunofluorescence showed the presence of both GR and MR in the hippocampal cell nuclei after dexamethasone exposure. The putative MR target gene JDP2 was consistently expressed at relatively low levels in the dexamethasone-treated brain samples. Gene expression showed substantial variation in MR/GR target gene expression in two different hippocampus tissue blocks from the same patient. ConclusionsDexamethasone may induce MR nuclear translocation in the human brain. Conclusions on in vivo effects on gene expression in the brain await the availability of more tissue of dexamethasone-treated patients.

Automated summary

This study aims to evaluate whether dexamethasone leads to reduced MR activation in the human brain. The results suggest that dexamethasone may induce MR nuclear translocation in the human brain. However, further research is needed to determine the specific effects of dexamethasone on gene expression in the brain.