New horizons for the role of selenium on cognitive function: advances and challenges

Cognitive deficits associated with oxidative stress and the dysfunction of the central nervous system are present in some neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Selenium (Se), an essential microelement, exhibits cognition-associated functions through selenoproteins mainly owing to its antioxidant property. Due to the disproportionate distribution of Se in the soil, the amount of Se varies greatly in various foods, resulting in a large proportion of people with Se deficiency worldwide. Numerous cell and animal experiments demonstrate Se deficiency-induced cognitive deficits and Se supplementation-improved cognitive performances. However, human studies yield inconsistent results and the mechanism of Se in cognition still remains elusive, which hinder the further exploration of Se in human cognition. To address the urgent issue, the review summarizes Se-contained foods (plant-based foods, animal-based foods, and Se supplements), brain selenoproteins, mechanisms of Se in cognition (improvement of synaptic plasticity, regulation of Zn²⁺ level, inhibition of ferroptosis, modulation of autophagy and de novo synthesis of L-serine), and effects of Se on cognitive deficits, as well as consequently sheds light on great potentials of Se in the prevention and treatment of cognitive deficits.