Glucocorticoid Consumption Alters Selenium Homeostasis and Hippocampal Selenoprotein Levels

Abstract

Long-term elevation of glucocorticoid levels is detrimental to neurological function, causing disturbances in mood and memory. Multiple molecular mechanisms of action have been implicated, including the disruption of antioxidant defense systems. This study focused on the impact of glucocorticoids on selenoproteins, which include selenoenzymes with antioxidant functions, some of which are essential for proper brain function. We exposed C57/BL6 mice to long-term glucocorticoid administration and measured changes in selenoprotein levels and gene expression. To study the underlying mechanism of selenoprotein regulation, we used an immortalized mouse hippocampal cell line. We found that Glutathione peroxidase 1 and Selenoprotein S levels are altered by glucocorticoids in a manner that is dependent on selenium availability and differential activation of the glucocorticoid and mineralocorticoid receptors. Spatial transcriptomic analysis of mouse hippocampal sections suggests spatial and cell-specific changes to the selenoprotein transcriptome. Finally, brain selenoprotein levels may be indirectly decreased by glucocorticoids due to insufficient distribution of selenium to the brain. Thus, glucocorticoids demonstrate an ability to control selenoprotein levels both by acting directly on hippocampal cells as well as indirectly by disrupting the delivery of dietary selenium to the brain. Future work will determine the impact of selenium intake on glucocorticoid-induced neurological dysfunction and damage.

The authors' abstract, as published at the source. Antioxidants, 2026 · DOI ↗