Schweizer Ulrich, Bräuer Anja U, Köhrle Josef, Nitsch Robert, Savaskan Nicolai E
Neurobiology of Selenium, Neuroscience Research Center, Charité, University Medical School, Berlin, Germany.
Brain Res Brain Res Rev. 2004 Jul;45(3):164-78. doi: 10.1016/j.brainresrev.2004.03.004.
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.
近年来，分子生物学在认识硒（Se）及硒依赖酶作为脑功能调节因子方面做出了重大贡献。氧化应激增加被认为是包括帕金森病、中风和癫痫等在内的神经退行性疾病的发病机制之一。谷胱甘肽过氧化物酶（GPx）、硫氧还蛋白还原酶和一种甲硫氨酸亚砜还原酶是参与抗氧化防御以及细胞内氧化还原调节的硒依赖酶。动物体内硒缺乏与硒依赖酶活性降低有关，并导致神经退行性疾病模型中细胞损失增加。细胞GPx的基因失活会增加对神经毒素和脑缺血的敏感性。相反，由于硒供应增加或过表达导致的GPx活性增加会改善相同疾病模型的结果。硒蛋白P的基因失活会导致脑硒含量显著降低，这是通过饮食中硒缺乏所无法实现的，还会导致运动障碍和自发性癫痫发作。在此，我们综述了硒在生理和病理生理条件下对大脑的作用，并强调了近期的研究发现，这些发现为这种古老的必需微量元素开辟了新的前景。
