Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model
Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model
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DOI：
10.1016/j.neurobiolaging.2007.12.013
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发表时间：
2009-10-01
影响因子：
4.2
通讯作者：
Gibson, Guy E.
中科院分区：
文献类型：
--
作者：
Karuppagounder, Saravanan S.;Xu, Hui;Gibson, Guy E.
线粒体功能障碍、氧化应激和硫胺素依赖性酶的减少与包括阿尔茨海默病 (AD) 在内的多种神经系统疾病有关。实验性硫胺素缺乏症（TD）是减少脑中硫胺素依赖性酶活性的既定模型。 TD 会减少整个大脑中的硫胺素依赖性酶，但仅在特定丘脑区域产生时间依赖性选择性神经元损失、神经胶质活化、炎症、氧化代谢异常以及退化神经突簇。目前的研究测试了 TD 如何改变过度表达淀粉样前体蛋白 (APP) 双突变形式的 Tg19959 转基因小鼠的大脑病理学。 TD 加剧了转基因小鼠的淀粉样斑块病理，并使皮质、海马和丘脑中斑块所占的面积分别扩大了 50%、200% 和 200%。 TD 使 A beta(1-42) 水平增加约三倍，使 beta-CTF (C99) 水平增加 33%，使 β-分泌酶 (BACE1) 蛋白质水平增加 43%。 TD 引起斑块形成区域的炎症。因此，TD引起的氧化代谢、氧化应激和炎症的轻度损害会改变APP和/或Aβ的代谢，并促进斑块的积累，而与神经元损失或神经炎簇无关。 (C) 2008 Elsevier Inc. 保留所有权利。
Mitochondrial dysfunction, oxidative stress and reductions in thiamine-dependent enzymes have been implicated in multiple neurological disorders including Alzheimer's disease (AD). Experimental thiamine deficiency (TD) is an established model for reducing the activities of thiamine-dependent enzymes in brain. TD diminishes thiamine-dependent enzymes throughout the brain, but produces a time-dependent selective neuronal loss, glial activation, inflammation, abnormalities in oxidative metabolism and clusters of degenerating neurites in only specific thalamic regions. The present studies tested how TD alters brain pathology in Tg19959 transgenic mice over expressing a double mutant form of the amyloid precursor protein (APP). TD exacerbated amyloid plaque pathology in transgenic mice and enlarged the area occupied by plaques in cortex, hippocampus and thalamus by 50%, 200% and 200%, respectively. TD increased A beta(1-42) levels by about three fold, beta-CTF (C99) levels by 33% and beta-secretase (BACE1) protein levels by 43%. TD-induced inflammation in areas of plaque formation. Thus, the induction of mild impairment of oxidative metabolism, oxidative stress and inflammation induced by TD alters metabolism of APP and/or A beta and promotes accumulation of plaques independent of neuron loss or neuritic clusters. (C) 2008 Elsevier Inc. All rights reserved.