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Selenium and Neurodevelopment

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Selenium

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

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Abstract

Brain is a privileged organ regarding selenium accumulation and metabolism. The discovery of a neurological phenotype in selenoprotein P knockout mouse provided a new perspective on the function of selenoproteins in brain. Since then, genetic studies in mice have revealed that some selenoproteins are indispensable to normal brain function. Neurodegeneration of GABAergic interneurons (PV+ neurons and Purkinje cells in cerebellum) was observed in Trsp and Secisbp2 knockout mice. Gpx4 knockout mice showed a similar phenotype, which could indicate that Gpx4 is necessary for maintenance or development of GABAergic interneurons. Similarly, SelT has a protective role for dopaminergic neurons and Txnrd1 is involved in radial glia development.

Progress of genome sequencing methods allowed to uncover inborn errors in selenoproteins or their biosynthetic factors, which lead to developmental and degenerative diseases in humans. Thus, mutations in SEPSECS gene lead to pontocerebellar hypoplasia type 2D, a neurodegenerative disease. Sedaghatian disease is caused by GPX4 mutations. Some of these patients show malformations of the central nervous system. A homozygous mutation in the TXNRD1 causes generalized epilepsy. Hearing loss and impaired movement coordination were symptoms found in patients suffering from SECISBP2 syndrome.

This chapter highlights neurological diseases and phenotypes detected in mouse and patients with impaired selenoprotein expression in the brain. Similarities and differences between mouse models and human disease are discussed.

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Authors and Affiliations

  1. Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany

    Noelia Fradejas-Villar & Ulrich Schweizer

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  1. Noelia Fradejas-Villar
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  2. Ulrich Schweizer
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Correspondence to Ulrich Schweizer .

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  1. Research Unit: Analytical BioGeoChemistry, Helmholtz Zentrum München – German Research Center for Environmental Health GmbH, Neuherberg, Germany

    Bernhard Michalke

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Fradejas-Villar, N., Schweizer, U. (2018). Selenium and Neurodevelopment. In: Michalke, B. (eds) Selenium. Molecular and Integrative Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-95390-8_9

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