Selenium at the Neural Barriers: A Review.

Nikolay Solovyev,Bastian Blume,Bernhard Michalke,Evgenii Drobyshev

doi:10.3389/fnins.2021.630016

Abstract

Selenium (Se) is known to contribute to several vital physiological functions in mammals: antioxidant defense, fertility, thyroid hormone metabolism, and immune response. Growing evidence indicates the crucial role of Se and Se-containing selenoproteins in the brain and brain function. As for the other essential trace elements, dietary Se needs to reach effective concentrations in the central nervous system (CNS) to exert its functions. To do so, Se-species have to cross the blood–brain barrier (BBB) and/or blood–cerebrospinal fluid barrier (BCB) of the choroid plexus. The main interface between the general circulation of the body and the CNS is the BBB. Endothelial cells of brain capillaries forming the so-called tight junctions are the primary anatomic units of the BBB, mainly responsible for barrier function. The current review focuses on Se transport to the brain, primarily including selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, also known as apolipoprotein E receptor-2) dependent pathway, and supplementary transport routes of Se into the brain via low molecular weight Se-species. Additionally, the potential role of Se and selenoproteins in the BBB, BCB, and neurovascular unit (NVU) is discussed. Finally, the perspectives regarding investigating the role of Se and selenoproteins in the gut-brain axis are outlined.

Highlights

The crucial role of the essential trace element selenium (Se) for the brain was already reported in the study of Weber et al (1991) demonstrating the alleviation of intractable seizures in children with a low level of glutathione peroxidase (GPX) activity following Se supplementation
The current review focuses on Se transport to the brain, including, first of all, selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, known as apolipoprotein E receptor-2) dependent pathway, and supplementary transport routes of Se into the brain via low molecular weight Se-species
Individual selenoproteins are known to be involved in regulating inflammation and immunity

Summary

INTRODUCTION

The crucial role of the essential trace element selenium (Se) for the brain was already reported in the study of Weber et al (1991) demonstrating the alleviation of intractable seizures in children with a low level of glutathione peroxidase (GPX) activity following Se supplementation. A commonly accepted Se metabolism concept includes the transformation of dietary Se to hydrogen selenide (HSe−), which serves as an intermediate between reductive metabolism of Se and excretory pathways, i.e., water-soluble methylated Se compounds (Chatterjee et al, 2003; Ogra and Anan, 2009) and selenosugars (Juresa et al, 2006; Kuehnelt et al, 2006; Rayman et al, 2008). For a detailed description regarding Se absorption and metabolism, the reader is referred to the specialized reviews, e.g., Combs et al (2013), Roman et al (2014), Cardoso et al (2015), and Vindry et al (2018)

Selenium at the Neural Barriers

CONCLUSION AND PERSPECTIVES

Findings

AUTHOR CONTRIBUTIONS