Comparative Analysis of Selenocysteine Machinery and Selenoproteome Gene Expression in Mouse Brain Identifies Neurons as Key Functional Sites of Selenium in Mammals

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.

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salarL.) fed diets with graded levels of plant ingredients

“…In the present study, higher expression of this gene was observed in brain of fish fed diets with high substitution levels and thus lower Se contents, which could indicate an up-regulation in the biosynthesis of new SEP. Although in mammals transcriptional changes in the brain in response to Se are rare (65) , some studies in fish brain have found differential expression when Se was supplemented to the diet. For instance, Benner et al (66) found increased expression of secp43 in brain with increased dietary Se supplementation in zebrafish.…”

Production of Selenoprotein P (Sepp1) by Hepatocytes Is Central to Selenium Homeostasis

“…Sepp1 is expressed within the brain by astrocytes and likely by other cells (39,40). The Sepp1 receptor apoER2 is present on neurons (41), so it is possible that Sepp1 functions to maintain appropriate distribution of selenium among cells in the brain as it does among tissues in the body (Fig.…”

The Neuroprotective Functions of Selenoprotein M and its Role in Cytosolic Calcium Regulation

“…Additionally, because of the predicted location of SelM in the endoplasmic reticulum and recent studies indicating that another ER-localized selenoprotein, selenoprotein N, is required for ryanodine receptor calcium release channel activity in muscle (1,12). We hypothesized that SelM could play a role in regulating calcium release from ER calcium stores (37).…”