Physiopathological role of selenium and selenoprotein in neuropsychiatry disease

Abstract

Selenium is widely distributed throughout the body, but it is particularly well maintained in the brain, even upon prolonged dietary selenium deficiency. Increased oxidative stress has been proposed as a pathomechanism in brain diseases and disorders including, among others, epilepsy, obsessive-compulsive disorders, Parkinson's disease, stroke and depression. Glutathione peroxidases and thioredoxin reductases are selenium-dependent enzymes involved in antioxidant defense and intracellular redox regulation and modulation. Selenium depletion in animals is associated with decreased activities of selenium-dependent enzymes and leads to enhanced cell loss in models of neurodegenerative disease. Genetic inactivation of cellular glutathione peroxidases increases the sensitivity towards neurotoxins and brain ischemia. Conversely, increased glutathione peroxidases activity as a result of increased selenium supply or overexpression ameliorates the outcome in the same models of disease. Genetic inactivation of selenoprotein P leads to a marked reduction of brain selenium content, which has not been achieved by dietary selenium depletion and to a movement disorder and spontaneous seizures. Here we review the role of selenium for the neuropsychiatric disorders under physiopathological conditions.