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

Authors

Yan Zhang, University of Nebraska-LincolnFollow
You Zhou, University of Nebraska-LincolnFollow
Ulrich Schweizer, Neurobiology of Selenium, Neuroscience Research Center, Charite-Universitatsmedizin, 10117 Berlin, Germany
Nicolai E. Savaskan, Department of Neuromorphology, Brain Research Institute, ETH & University of Zurich, Winterthurerstrasse 190 CH-8057 Zurich, Switzerland
Deame Hua, University of Nebraska-Lincoln
Jonathan Kipnis, University of Virginia
Dolph L. Hatfield, Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MarylandFollow
Vadim N. Gladyshev, University of Nebraska-LincolnFollow

Date of this Version

1-25-2008

Comments

Published in THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 283, NO. 4, pp. 2427–2438, January 25, 2008. Copyright 2008. Used by permission. Printed in the U.S.A.

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.