Selenium, selenoproteins and brain function

Summary

After the discovery of selenium (Se) as an essential trace element, direct evidence that Se plays a role in brain function remained relatively scarce for many years. This was probably due to the remarkable stability of brain Se levels during times of dietary Se restriction in experimental animals. In these experiments, activities of the first known Sedependent enzymes, e.g. glutathione peroxidase (GPX), thioredoxin reductase (TrxR), and deiodinase (Dio), were also little changed in the brains of rodents fed Se-defieient diets for extended periods of time. Thus, the lack of spontaneous neurological deficits seemed to exclude an important role for Se in brain function. This notion remained largely unchanged despite the purification of selenoprotein P (SePP) from serum as a neurotrophic factor for cultured neurons and the finding that selenite is an essential component of media for in vitro culture of central neurons. Only later experiments revealed that Se-deficiency exacerbated the outcome of neurological disease in certain animal models. Oxidative stress is considered to play a role in neurodegenerative processes, and GPXl-transgenic mice provided the first molecular proof for an involvement of selenoproteins in such conditions. Then, gene targeting of SePP led to clear-cut spontaneous neurological deficits in Se-deficient animals and placed SePP at center stage for the priviledged Se supply to the brain. Whether impaired expression of selenoproteins in human brain contributes to the incidence or severity of neurodegenerative disease remains to be established. Still, available evidence already suggests that selenoproteins are playing important roles for brain development, function, and disease in mice - and also most likely in humans.