极低频电磁辐射(50Hz)遍及现代生活和工作环境的各个角落，其对健康的危害已成为公众和国内外学者关注的热点问题之一。早在上世纪90年代，流行病学调查显示50Hz极低频电磁辐射是阿尔兹海墨病(AD)高发的危险因素，但近20年来仍未获得实验室研究的支持。国内外研究发现AD患者神经细胞Tau蛋白过度磷酸化，而其O-GlcNAc糖基化水平明显降低。我们前期研究初步显示50Hz磁场暴露也可引起同样效应，但机制不清。本项目拟以正常小鼠和AD小鼠为动物模型，以原代培养海马神经元和N2a/APP细胞株为细胞模型，系统研究50Hz磁场暴露对Tau蛋白磷酸化和O-GlcNAc糖基化平衡状态的影响，并探讨CDK5和GSK3β信号途径、蛋白磷酸酶(PP1、PP2A)、OGT、OGA、氨基己糖生物合成途径关键酶-GFAT在该平衡失衡中的作用地位，筛选关键分子事件，为寻找50Hz磁场暴露致神经损伤防治新靶点提供线索。

Nearly 2 decades ago, epidemiological studies suggested that ELF-EMF(50 Hz) is a high risk factor for Alzheimer's disease (AD) pathogenesis. However, this presumption is not still completely supported by laboratory researches. Enormous studies have showed that tau protein is hyperphosphorylated at multiple sites, and meanwhile the O-linked N-acetylglucosamine (O-GlcNAc) glycosylation of tau protein is inhibited in brain neurons of AD patients. Our recent primary research showed the same effects (phenomenon), the imbalance of phosphorylation and O-GlcNAc glycosylation of tau protein, in cortical and hippocampal neurons of mice exposed to 50 Hz magnetic field. But the molecular mechanism is unclear. By selecting normal mice (C57BL/6 mice) and AD mice (APP/PSN mice) as animal models, and primary cultured hippocampal neurons and N2a/APP cell line as cell models, this project intends to systematically study the effects of 50 Hz magnetic field exposure on the balance of phosphorylation and O-GlcNAc glycosylation of tau protein, and further study the roles of cyclin dependent kinase 5 (CDK5) signal pathway, phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/ glycogen-synthase kinase-3β(GSK-3β) signal pathway,protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A),O-β-N-acetylglucosaminyltransferase (OGT), O-β-N-acetylglucosaminidase (OGA),glutamine:fructose-6-phosphate amido-transferase (GFAT, the rate-limiting enzyme acting in the hexosamine biosynthetic pathway), and find the key molecule events in the imbalance of phosphorylation and O-GlcNAc glycosylation of tau protein induced by 50 Hz magnetic field exposure. This project is going to shed light on the possible strategies for preventing and curing the neuron injury induced by 50 Hz magnetic field exposure.