Abstract
Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss. To address the basis for the critical role of Se in brain function, we carried out comparative gene expression analyses for the complete selenoproteome and associated biosynthetic factors. Using the Allen Brain Atlas, we evaluated 159 regions of adult mouse brain and provided experimental analyses of selected selenoproteins. All 24 selenoprotein mRNAs were expressed in the mouse brain. Most strikingly, neurons in olfactory bulb, hippocampus, cerebral cortex, and cerebellar cortex were exceptionally rich in selenoprotein gene expression, in particular in GPx4, SelK, SelM, SelW, and Sep15. Over half of the selenoprotein genes were also expressed in the choroid plexus. A unique expression pattern was observed for one of the highly expressed selenoprotein genes, SelP, which we suggest to provide neurons with Se. Cluster analysis of the expression data linked certain selenoproteins and selenocysteine machinery genes and suggested functional linkages among selenoproteins, such as that between SelM and Sep15. Overall, this study suggests that the main functions of selenium in mammals are confined to certain neurons in the brain.
Highlights
Dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss
Global Analysis of Selenoprotein and Sec Machinery Gene Expression in Mouse Brain—Original in situ hybridization (ISH) image data could be identified in the Allen Brain Atlas (ABA) dataset for 23 selenoprotein genes and 5 Sec machinery genes
The remaining mouse selenoprotein gene (SelH), was not represented in the ABA dataset, but it was detected in mouse brain in previous studies [29], and we experimentally verified its expression during development in rat brain
Summary
For more than 21,000 genes in adult mouse brain [26]. The dataset provides both mRNA in situ hybridization (ISH) data and a detailed reference atlas. This resource represents a comprehensive platform for exploring gene expression in the brain and can be used to examine and compare expression of all selenoprotein genes. We normalized and quantified the original gene expression data and clustered them by hierarchical cluster analysis to identify linkages among selenoproteins and between selenoproteins and the Sec machinery. Cluster analysis allowed us to identify functional links among selenoproteins and their biosynthetic machinery. The results of this study open new opportunities for research on Se, an essential trace element, and are important for understanding the relationship between Se and brain function
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