Dietary selenium supplementation reduces susceptibility to depression-like behaviors in mice by increasing MSRB1 expression in hippocampal astrocytes

The global burden of major depressive disorder (MDD) is increasing. Preclinical and clinical studies have indicated a close association between levels of trace elements and the incidence of MDD. However, little is known about the association between selenium levels and MDD. Methionine sulfoxide reductase B1 (MSRB1) is a selenoprotein regulated by dietary selenium levels that can indirectly clear reactive oxygen species (ROS). Here we show that supplementing the diet with L-selenomethionine, the most common organic selenium compound in organisms, effectively reduces the susceptibility of mice to depressive-like behavior induced by unpredictable chronic mild stress (CUMS). Furthermore, by knocking down MSRB1 in primary astrocytes and mouse hippocampi, we demonstrate that L-selenomethionine exerts its protective effect by increasing MSRB1 levels in hippocampal astrocytes. MSRB1 reduces ROS-induced neuroinflammation in astrocytes by indirectly clearing ROS. Our findings not only reveal a role for dietary selenium in regulating the susceptibility of mice to CUMS-induced depressive-like behaviors but also further identify the specific selenoprotein mediating this effect. These findings provide a potential dietary approach for preventing MDD in clinical practice and the motivation for further preclinical studies.