rTg4510转基因tau模型小鼠的中枢及外周葡萄糖代谢改变的研究  

Brain and Peripheral Glucose Metabolic Changes in A Tau Transgenic Mouse Model

作　　者：张梦伟 郁文博 肖保国[2] 王坚 ZHANG Meng-wei;YU Wen-bo;XIAO Bao-guo;WANG Jian(Department of Neurology,Huashan Hospital,Fudan University,Shanghai 200040,China;Institute of Neurology,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院神经内科,上海200040 [2]复旦大学神经病学研究所,上海200040

出　　处：《中国临床神经科学》2023年第1期9-15,共7页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金面上项目(编号:81771372)。

摘　　要：目的探究tau病理背景下小鼠中枢及外周葡萄糖代谢的改变及其发生机制。方法选取12月龄rTg4510小鼠(rTg4510组)及同窝对照(nTg)小鼠(nTg组)。使用行为学方法检测其认知和运动变化,18氟-脱氧葡萄糖正电子发射断层(18F-FDGPET)显像评估脑葡萄糖代谢,腹腔葡萄糖耐量实验(IPGTT)和腹腔胰岛素耐量实验(IPITT)评估外周葡萄糖稳态,酶联免疫吸附试验检测中枢及外周胰岛素水平,Western blot法观察海马胰岛素相关信号蛋白胰岛素受体底物1(IRS-1)表达水平。免疫荧光及Western blot法检测葡萄糖转运体亚型1(Glut1)蛋白表达水平。结果与nTg组比较,rTg4510组小鼠呈现运动活跃、认知损害和焦虑减少等行为学表现;18F-FDGPET显示皮质和海马明显低代谢,伴有外周胰岛素敏感性增加,外周和中枢胰岛素水平相当;海马IRS-1和Glut1蛋白表达水平无显著改变。结论rTg4510小鼠存在脑葡萄糖代谢降低及外周胰岛素敏感性增加;外周和中枢胰岛素水平、IRS-1、Glut1蛋白水平无变化,提示rTg4510小鼠呈现的脑18F-FDG PET低代谢与胰岛素信号受损或Glut1表达水平无相关性。Aim To investigate the changes in the brain and peripheral glucose metabolism in mice with tau pathology and explore its possible mechanism.Methods 12-month-old rTg4510 mice,and nontransgenic littermate control(nTg)mice were selected,behavioral tests were used to detect their cognitive and motor abnormalities,and cerebral glucose metabolism was evaluated by 18F-FDG PET.The glucose tolerance test and insulin tolerance test were used to assess peripheral glucose homeostasis.Brain and serum insulin levels were measured by ELISA.Insulin-related signaling protein,insulin receptor substrate 1(IRS-1)in the hippocampus,was evaluated by Western blot.Immunofluorescence and Western blot were used to detect the expression of glucose transporter isoform 1(Glut1).Results Compared with nontransgenic littermates,rTg4510 mice showed behavioral manifestations such as locomotor hyperactivity,impaired cognition,and reduced anxiety.18F-FDG-PET showed significant hypometabolism in the hippocampus and cortex of rTg4510 mice with improved insulin sensitivity and comparable peripheral and central insulin levels.The expression levels of IRS-1 and Glut1 in the hippocampus showed no significant difference.Conclusion There was reduced cerebral glucose metabolism and increased insulin sensitivity in rTg4510 mice.Peripheral and central insulin levels,IRS-1,and Glut1 protein expression levels were unchanged,suggesting that cerebral glucose hypometabolism presented by rTg4510 was not associated with impaired insulin signaling or altered Glut1 expression levels.

关 键 词：tau蛋白 18氟-脱氧葡萄糖正电子发射断层显像 脑葡萄糖代谢 胰岛素 胰岛素受体底物1 葡萄糖转运体亚型1 

分 类 号：R741[医药卫生—神经病学与精神病学]