Butterworth Roger F
Neuroscience Research Unit, Hôpital Saint-Luc (CHUM), 1058 St-Denis Street, Montreal, Quebec H2X 3J4, Canada.
Nutr Res Rev. 2003 Dec;16(2):277-84. doi: 10.1079/NRR200367.
Thiamin plays a key role in the maintenance of brain function. Thiamin diphosphate is cofactor for several enzymes involved in glucose metabolism whereas thiamin triphosphate has distinct properties at the neuronal membrane. Thiamin metabolism in the brain is compartmented between neurons and neighbouring glial cells. Thiamin deficiency is commonly encountered in severe malnutrition associated with chronic alcoholism, HIV-AIDS and gastrointestinal disease where it frequently results in Wernicke's encephalopathy (the Wernicke-Korsakoff syndrome). Wernicke's encephalopathy is severely underdiagnosed according to clinical criteria in both alcoholic and HIV-AIDS patients. Magnetic resonance imaging reveals bilateral ventricular enlargement, mammillary body atrophy and cerebellar degeneration indicative of selective neuronal loss that is characteristic of Wernicke's encephalopathy. Several mechanisms have been proposed to explain this selective loss of neurons including a cerebral energy deficit resulting from reductions in activity of thiamin diphosphate-dependent enzymes, oxidative stress and N-methyl-D-aspartate receptor-mediated excitotoxicity. Both microglia and perivascular endothelial cells are sources of NO and oxidative stress in thiamin deficiency. Decreased activities of thiamin diphosphate-dependent enzymes (in particular alpha-ketoglutarate dehydrogenase) have also been reported in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases independent of patient malnutrition. In these cases, decreased activities result from direct toxic actions of oxidative stress and beta-amyloid produced as part of the neuronal cell death cascade in these disorders.
硫胺素在维持脑功能方面起着关键作用。硫胺素二磷酸是参与葡萄糖代谢的几种酶的辅酶，而硫胺素三磷酸在神经元膜上具有独特的性质。大脑中的硫胺素代谢在神经元和相邻的神经胶质细胞之间是分隔的。硫胺素缺乏常见于与慢性酒精中毒、艾滋病毒-艾滋病和胃肠道疾病相关的严重营养不良中，在这些情况下，它经常导致韦尼克脑病（韦尼克-科尔萨科夫综合征）。根据临床标准，酒精性和艾滋病毒-艾滋病患者中的韦尼克脑病严重漏诊。磁共振成像显示双侧脑室扩大、乳头体萎缩和小脑变性，这表明存在选择性神经元丢失，这是韦尼克脑病的特征。已经提出了几种机制来解释这种神经元的选择性丢失，包括硫胺素二磷酸依赖性酶活性降低导致的脑能量不足、氧化应激和N-甲基-D-天冬氨酸受体介导的兴奋性毒性。在硫胺素缺乏时，小胶质细胞和血管周围内皮细胞都是一氧化氮和氧化应激的来源。在阿尔茨海默病和帕金森病等神经退行性疾病中，也有报道称硫胺素二磷酸依赖性酶（特别是α-酮戊二酸脱氢酶）的活性降低，而与患者营养不良无关。在这些情况下，活性降低是由氧化应激和β-淀粉样蛋白的直接毒性作用导致的，这些是这些疾病中神经元细胞死亡级联反应的一部分。
