Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice

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	Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice
	Pan, Xiaoli ; Gong, Neng ; Zhao, Jing ; Yu, Zhe ; Gu, Fenghua ; Chen, Jia ; Sun, Xiaojing ; Zhao, Lei ; Yu, Meijing ; Xu, Zhiru ; Dong, Wenxin ; Qin, Yan ; Fei, Guoqiang ; Zhong, Chunjiu ; Xu, Tian-Le(徐天乐)
刊名	BRAIN
	2010
卷号	133 期号:pt 5 页码:1342-1351
关键词	Alzheimer benfotiamine thiamine glycogen synthase kinase-3 POSITRON-EMISSION-TOMOGRAPHY ALZHEIMERS-DISEASE THIAMINE-DEFICIENCY HYPERGLYCEMIC DAMAGE OXIDATIVE STRESS PHOSPHATE-ESTERS PROTEIN BRAIN RISK DERIVATIVES
ISSN号	0006-8950
通讯作者	Zhong, CJ (reprint author), Zhongshan Hosp, Dept Neurol, Shanghai 200032, Peoples R China,zhongcj@163.com
英文摘要	Reduction of glucose metabolism in brain is one of the main features of Alzheimer's disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3 alpha and -3 beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment.
学科主题	Neurosciences & Neurology
收录类别	SCI
资助信息	Science and Technology Commission of Shanghai Municipality[07DJ14005, 09DZ1950400, 09XD1404900]; National Natural Science Foundation of China[30830035]; State Scientific & Technological Ministry of China[2009ZX09301-011]; Institutes of Brain Science of Fudan University; State Key Laboratory of Neuroscience
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/331001/1595]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Pan, Xiaoli,Gong, Neng,Zhao, Jing,et al. Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice[J]. BRAIN,2010,133(pt 5):1342-1351.
APA	Pan, Xiaoli.,Gong, Neng.,Zhao, Jing.,Yu, Zhe.,Gu, Fenghua.,...&Xu, Tian-Le.(2010).Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice.BRAIN,133(pt 5),1342-1351.
MLA	Pan, Xiaoli,et al."Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice".BRAIN 133.pt 5(2010):1342-1351.