Exposure to Pyrithiamine Increases beta-Amyloid Accumulation, Tau Hyperphosphorylation, and Glycogen Synthase Kinase-3 Activity in the Brain

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	Exposure to Pyrithiamine Increases beta-Amyloid Accumulation, Tau Hyperphosphorylation, and Glycogen Synthase Kinase-3 Activity in the Brain
	Zhao, Jing ; Sun, Xiaojing ; Yu, Zhe ; Pan, Xiaoli ; Gu, Fenghua ; Chen, Jia ; Dong, Wenxin ; Zhao, Lei ; Zhong, Chunjiu
刊名	NEUROTOXICITY RESEARCH
	2011
卷号	19 期号:4 页码:575-583
关键词	Alzheimer's disease Thiamine deficiency Pyrithiamine Glycogen synthase kinase-3 POSITRON-EMISSION-TOMOGRAPHY FAMILIAL ALZHEIMERS-DISEASE THIAMINE-DEPENDENT ENZYMES TRANSGENIC MICE WERNICKES ENCEPHALOPATHY INSULIN-RESISTANCE PRECURSOR PROTEIN MOUSE MODELS A-BETA DEFICIENCY
ISSN号	1029-8428
通讯作者	Zhong, CJ (reprint author), Fudan Univ, Zhongshan Hosp, Dept Neurol, Shanghai 200032, Peoples R China,zhongcj@163.com
英文摘要	Decreased thiamine-dependent enzyme activity and/or thiamine deficiency (TD) have been linked to Alzheimer's disease (AD). In this study, we administered pyrithiamine, an anti-thiamine compound, to both APP/PS1 transgenic mice and wild-type littermate control mice; alternatively, we induced TD by thiamine-depleted diet. Pyrithiamine treatment and diet-induced TD impaired the memory of wild-type mice, but had little effect on APP/PS1 mice. Pathophysiologically, pyrithiamine treatment and diet-induced TD aggravated beta-amyloid accumulation in the brain. This was demonstrated by increased beta-amyloid in the brains of wild-type mice using ELISA and by the number of amyloid plaques in the brains of APP/PS1 transgenic mice using immunochemical staining. Also, enhanced numbers of phosphorylated Tau-positive cells were observed in both APP/PS1 transgenic and wild-type mice. Furthermore, pyrithiamine decreased the phosphorylation rates of glycogen synthase kinase (GSK)-3 beta and raised its enzymatic activity, but had little influence on GSK-3 alpha. Diet-induced TD reduced the phosphorylated rates and increased the activities of GSK-3, GSK-3 alpha, and GSK-3 beta. These results suggest that when sufficient thiamine supplement is administered, pyrithiamine can cause AD-like pathological alterations similar to that of diet-induced TD.
学科主题	Neurosciences & Neurology
收录类别	SCI
资助信息	Science and Technology Commission of Shanghai Municipality[09DZ1950400, 10430709600]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1543]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Zhao, Jing,Sun, Xiaojing,Yu, Zhe,et al. Exposure to Pyrithiamine Increases beta-Amyloid Accumulation, Tau Hyperphosphorylation, and Glycogen Synthase Kinase-3 Activity in the Brain[J]. NEUROTOXICITY RESEARCH,2011,19(4):575-583.
APA	Zhao, Jing.,Sun, Xiaojing.,Yu, Zhe.,Pan, Xiaoli.,Gu, Fenghua.,...&Zhong, Chunjiu.(2011).Exposure to Pyrithiamine Increases beta-Amyloid Accumulation, Tau Hyperphosphorylation, and Glycogen Synthase Kinase-3 Activity in the Brain.NEUROTOXICITY RESEARCH,19(4),575-583.
MLA	Zhao, Jing,et al."Exposure to Pyrithiamine Increases beta-Amyloid Accumulation, Tau Hyperphosphorylation, and Glycogen Synthase Kinase-3 Activity in the Brain".NEUROTOXICITY RESEARCH 19.4(2011):575-583.