A comprehensive review on the neuropathophysiology of selenium

As an essential micronutrient, selenium (Se) exerts its biological function as a catalytic entity in a variety of enzymes. From a toxicological perspective, however, Se can become extremely toxic at concentrations slightly above its nutritional levels. Over the last few decades, there has been a growing level of concern worldwide regarding the adverse effects of both inorganic and organic Se compounds on a broad spectrum of neurological functions. A wealth of evidence has shown that exposure to excess Se may compromise the normal functioning of various key proteins, neurotransmitter systems (the glutamatergic, dopaminergic, serotonergic, and cholinergic systems), and signaling molecules involved in the control and regulation of cognitive, behavioral, and neuroendocrine functions. Elevated Se exposure has also been suspected to be a risk factor for the development of several neurodegenerative and neuropsychiatric diseases. Nonetheless, despite the various deleterious effects of excess Se on the central nervous system (CNS), Se neurotoxicity and negative behavioral outcomes are still disregarded at the expense of its beneficial health effects. This review focuses on the current state of knowledge regarding the neurobehavioral effects of Se and discusses its potential mode of action on different aspects of the central and peripheral nervous systems. This review also provides a brief history of Se discovery and uses, its physicochemical properties, biological roles in the CNS, environmental occurrence, and toxicity. We also review potential links between exposure to different forms of Se compounds and aberrant neurobehavioral functions in humans and animals, and identify key knowledge gaps and hypotheses for future research. [Display omitted] •Selenium is an essential micronutrient but can be toxic at higher levels.•Both inorganic and organic selenium species adversely affect the nervous system.•Oxidative stress seems to be the main driver of selenium neurotoxicity.•Selenium can disrupt several neurotransmitters and neuromodulatory systems.•Exposure to excess selenium can be a risk factor for various brain disorders.