Selenium and brain function: a poorly recognized liaison.
Molecular biology has recently contributed significantly to the recognition of selenium (Se)2 and Se-dependent enzymes as modulators of brain function. Increased oxidative stress has been proposed as a pathomechanism in neurodegenerative diseases including, among others, Parkinson's disease, stroke, and epilepsy. Glutathione peroxidases (GPx), thioredoxin reductases, and one methionine-sulfoxide-reductase are selenium-dependent enzymes involved in antioxidant defense and intracellular redox regulation and modulation. Selenium depletion in animals is associated with decreased activities of Se-dependent enzymes and leads to enhanced cell loss in models of neurodegenerative disease. Genetic inactivation of cellular GPx increases the sensitivity towards neurotoxins and brain ischemia. Conversely, increased GPx activity as a result of increased Se supply or overexpression ameliorates the outcome in the same models of disease. Genetic inactivation of selenoprotein P leads to a marked reduction of brain Se content, which has not been achieved by dietary Se depletion, and to a movement disorder and spontaneous seizures. Here we review the role of Se for the brain under physiological as well as pathophysiological conditions and highlight recent findings which open new vistas on an old essential trace element.
Schweizer
Ulrich
U
Neurobiology of Selenium, Neuroscience Research Center, Charité, University Medical School, Berlin, Germany.
Bräuer
Anja U
AU
Köhrle
Josef
J
Nitsch
Robert
R
Savaskan
Nicolai E
NE
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001921:Brain / Q000502:physiology*; D002986:Clinical Trials as Topic; D003409:Congenital Hypothyroidism / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D016571:Neural Networks, Computer; D011506:Proteins / Q000378:metabolism*; D012643:Selenium / Q000502:physiology*; D051149:Selenoprotein P; D051140:Selenoproteins; D015398:Signal Transduction / Q000502:physiology
D000975:Antioxidants; D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium