The brain selenoproteome: priorities in the hierarchy and different levels of selenium homeostasis in the brain of selenium‐deficient rats

Abstract

The application of radionuclides for the localization of essential trace elements in vivo and the characterization of their binding proteins is a story of intermittently made improvements of the techniques used for their detection. In this study we present the use of neutron activation analysis and different autoradiographic imaging methods including real‐time digital autoradiography to reveal new insights in the hierarchy of selenium homeostasis. Selenoproteins containing the essential trace element selenium play important roles in the CNS. Although the CNS does not show the highest selenium concentration in the case of selenium‐sufficient supply in comparison with other organs, it shows a high priority for selenium uptake and retention in the case of dietary selenium deficiency. To characterize the hierarchy of selenium supply in the brain, in vivo radiotracer labeling with 75Se in rats with different selenium status was combined with autoradiographic detection of 75Se in brain tissue sections and 75Se‐labeled selenoproteins after protein separation by two‐dimensional gel electrophoresis. This study demonstrates significant differences in the uptake of 75Se into the brain of rats with different selenium status. A brain region‐specific uptake pattern of the radiotracer 75Se in selenium‐deficient rats could be revealed and the CSF was identified as a key part of the brain selenium homeostasis.

Selenium, selenoproteins and neurodegenerative diseases

“…Imaging using a 75 Se radiotracer combined with autoradiographic localisation and proteomic analysis to profile Se levels in different brain regions of rats fed a Se-replete diet revealed that Se was enriched in choroid plexus, putamen, parietal inferior lobule and occipital cortex. 35 This observation has been reflected in human brains, where the highest Se concentration occurs in grey matter, with the putamen, parietal inferior lobule and occipital cortex in particular, while the lowest levels are found in the cerebellum and medulla. 36 The mechanism that maintains Se levels in the brain at the expense of other organs, even during times of deprivation, is mainly orchestrated by SelP, which is recognised as the most important Se supply to different tissue types.…”

“…2 (a) SelP, the master protein driving Se bioavailability is synthesised in the liver from both inorganic and organoselenium compounds accessible through dietary sources. At the blood-brain barrier, SelP releases Se into the CNS via the ApoER2 receptor, which is in turn incorporated into newlyformed SelP in astrocytes (figure adapted from Burk et al 35 ), or is transported directly to neurons (dashed arrow). SelP is made available to neurons via the same membrane-bound ApoER2, where additional selenoproteins essential to neurological function (blue box) are biosynthesised.…”

“…Selenium deficient rats presented approximately 29% lower Se levels in the brain compared to animals with a sufficient Se supply, which is not nearly as dramatic as the 99% and 92% decrease in Se concentration in the liver and kidneys of deficient animals. 34 Se distribution is heterogeneous among different brain regions, and grey matter appears to have preference for greater uptake. Imaging using a 75 Se radiotracer combined with autoradiographic localisation and proteomic analysis to profile Se levels in different brain regions of rats fed a Se-replete diet revealed that Se was enriched in choroid plexus, putamen, parietal inferior lobule and occipital cortex.…”

Selenium speciation in paired serum and cerebrospinal fluid samples of sheep

“…That underlines a high priority for Se uptake and retention in the CSF during marginal dietary Se supplementation. CSF was identified before as a key part of the brain Se homeostasis showing the highest uptake of the applied 75 Se in the brain, suggesting a high turnover rate of Se in the ventricular system [11].…”

“…The authors assumed that the Se uptake is regulated by a brain region-specific expressed receptor and that the expression of the receptor is nutritionally regulated by the Se status. Within the CNS, CSF showed the highest uptake of the applied 75 Se (intraperitoneal injection) and the authors suggested a high turnover rate of this Se in the ventricular system [11].…”