The ability of the body to maintain homeostasis requires constant communication between the brain and peripheral tissues. Different organs produce signals, often in the form of hormones, which are detected by the hypothalamus. In response, the hypothalamus alters its regulation of bodily processes, which is achieved through its own pathways of hormonal communication. The generation and transmission of the molecules involved in these bi-directional axes can be affected by redox balance. The essential trace element selenium is known to influence numerous physiological processes, including energy homeostasis, through its various redox functions. Selenium must be obtained through the diet and is used to synthesize selenoproteins, a family of proteins with mainly antioxidant functions. Alterations in selenium status have been correlated with homeostatic disturbances in humans and studies with animal models of selenoprotein dysfunction indicate a strong influence on energy balance. The relationship between selenium and energy metabolism is complicated, however, as selenium has been shown to participate in multiple levels of homeostatic communication. This review discusses the role of selenium in the various pathways of communication between the body and the brain that are essential for maintaining homeostasis.

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.