中文摘要：

为了探讨大脑中葡萄糖摄取和代谢障碍在阿尔茨海默病（Alzheimer＇s disease，AD）神经退行性病变中的作用，将昆明种小鼠进行饥饿和再喂食处理，并使用多种磷酸化tau蛋白特异性的抗体和蛋白O-GIcNAc糖基化特异性抗体进行检测，观察饥饿及恢复喂养后不同时间点大脑皮质中tau蛋白糖基化及多个位点磷酸化的变化．结果显示：饥饿处理引起小鼠大脑皮质中总蛋白和tau蛋白的O-GIcNAc糖基化水平降低，同时tau蛋白磷酸化水平升高，饥饿引起的tau O-GIcNAe糖基化和磷酸化改变均在恢复进食后逆转成正常水平．该研究结果提示：大脑中tau蛋白的磷酸化和O-GIcNAc糖基化之间存在相互调节，脑中葡萄糖代谢障碍可能通过下调tau蛋白O-GIcNAc糖基化水平使tau蛋白产生异常过度磷酸化，进而促发AD的病理进程．这一结果为在早期阶段通过逆转tau蛋白异常过度磷酸化治疗AD成为可能提供了实验基础．

英文摘要：

To explore the role of impaired brain glucose uptake/metabolism in neurodegeneration of Alzheimer＇s disease （AD）, the relationship between an impaired brain glucose uptake/metabolism （down-regulation of tau O-GlcNAcylation） and the abnormal hyperphosphorylation of tau was investigated in fasting mice. It was found that fasting caused reduction of tau O-GlcNAcylation and a concomitant increase of tau phosphorylation at several hyperphosphorylation sites as seen in AD brain. Furthermore, hyperphosphorylation of tau induced by fasting was reversible in the brain after re-feeding. These findings provide a novel mechanism explaining how impaired brain glucose uptake/metabolism may contribute to AD-like tau hyperphosphorylation and also suggest feasibility to treat AD by reversing abnormal hyperphosphorylation of tau at early stages of the disease.