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Title: Exposure to Pyrithiamine Increases beta-Amyloid Accumulation, Tau Hyperphosphorylation, and Glycogen Synthase Kinase-3 Activity in the Brain
Author: Zhao, Jing ; Sun, Xiaojing ; Yu, Zhe ; Pan, Xiaoli ; Gu, Fenghua ; Chen, Jia ; Dong, Wenxin ; Zhao, Lei ; Zhong, Chunjiu
Source: NEUROTOXICITY RESEARCH
Issued Date: 2011
Volume: 19, Issue:4, Pages:575-583
Keyword: 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
Subject: Neurosciences & Neurology
Corresponding Author: Zhong, CJ (reprint author), Fudan Univ, Zhongshan Hosp, Dept Neurol, Shanghai 200032, Peoples R China,zhongcj@163.com
English Abstract: 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.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1543
Appears in Collections:神经所(总)_期刊论文

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Zhao, Jing; Sun, Xiaojing; Yu, Zhe; Pan, Xiaoli; Gu, Fenghua; Chen, Jia; Dong, Wenxin; Zhao, Lei; Zhong, Chunjiu.Exposure to Pyrithiamine Increases beta-Amyloid Accumulation, Tau Hyperphosphorylation, and Glycogen Synthase Kinase-3 Activity in the Brain,NEUROTOXICITY RESEARCH,2011,19(4):575-583
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