Role of mitochondrial dysfunction and oxidative stress in the pathogenesis of selective neuronal loss in Wernicke’s encephalopathy

被引:0
作者
Paul Desjardins
Roger F. Butterworth
机构
[1] University of Montreal,Neuroscience Research Unit, CHUM (Hôpital St
来源
Molecular Neurobiology | 2005年 / 31卷
关键词
Thiamine deficiency; Wernicke-Korsakoff; oxidative stress; mitochondrial dysfunction; neuronal cell death; reactive oxygen species; nitric oxide synthase; thalamic lesions;
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摘要
Thiamine deficiency results in Wernicke’s encephalopathy and is commonly encountered in chronic alcoholism, gastrointestinal diseases, and HIV AIDS. The earliest metabolic consequence of thiamine deficiency is a selective loss in activity of the thiamine diphosphate-dependent enzyme α-ketoglutarate dehydrogenase (α-KGDH), a rate-limiting tricarboxylic acid cycle enzyme. Thiamine deficiency is characterized neuropathologically by selective neuronal cell death in the thalamus, pons, and cerebellum. The cause of this region-selective neuronal loss is unknown, but mechanisms involving cellular energy failure, focal lactic acidosis, and NMDA receptor-mediated excitotoxicity have classically been implicated. More recently, evidence supports a role for oxidative stress. Evidence includes increased endothelial nitric oxide synthase, nitrotyrosine deposition, microglial activation, and lipid peroxidation. Reactive oxygen species production results in decreased expression of astrocytic glutamate transporters and decreased activities of α-KGDH, resulting in an amplification of cell death mechanisms in thiamine deficiency.
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页码:17 / 25
页数:8
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