复旦大学附属中山医院神经内科钟春玖教授通过长达10年潜心研究，发现一种新型维生素B1衍生物能显着改善老年性痴呆小鼠模型的认知功能和病理损害。
日前，国际著名学术杂志BRAIN发表了钟春玖教授与中科院神经科学研究所徐天乐研究员合作研究的成果。这标志着我国在防治老年性痴呆研究方面获得新的突破。
钟春玖教授领衔的课题组利用老年性痴呆转基因小鼠模型研究发现，一个新型维生素B1衍生物治疗八周后，能显着增加老年性痴呆转基因小鼠模型在Morris水迷宫第Ⅳ象限穿台次数和停留时间，减少痴呆小鼠脑内老年斑和神经纤维缠结数量，具有剂量?效应关系。钟春玖教授领军的课题组与中国科学院徐天乐研究员领军的课题组合作的实验结果还表明，该新型维生素B1衍生物是通过非维生素B1依赖的作用机制发挥作用的，其药理作用与显着增加糖合酶－3α和3β的磷酸化，抑制糖合酶－3活性有关。
推荐原文出处：
Brain 2010 133(5):1342-1351; doi:10.1093/brain/awq069
Powerful beneficial effects of benfotiamine on cognitive impairment and β-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice
Xiaoli Pan1,*, Neng Gong2,*, Jing Zhao1, Zhe Yu2, Fenghua Gu3, Jia Chen3, Xiaojing Sun1, Lei Zhao1, Meijing Yu3, Zhiru Xu3, Wenxin Dong3, Yan Qin3, Guoqiang Fei1, Chunjiu Zhong1 and Tian-Le Xu2
1 Department of Neurology, Zhongshan Hospital " Shanghai Medical College, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China 2 Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China
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 and -3β, 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.
