兴奋性氨基酸受体的激活介导冷水应激诱导的tau蛋白磷酸化(英文)  

The Activation of Excitatory Amino Acid Receptors Is Involved in tau Phosphorylation Induced by Cold Water Stress

作　　者：武凤英[1] 冯琼[1] 程敏[1] 闫洁[1] 许玉霞[1] 朱粹青[1] 

机构地区：[1]复旦大学上海医学院医学神经生物学国家重点实验室,上海200032

出　　处：《生物化学与生物物理进展》2010年第5期510-516,共7页Progress In Biochemistry and Biophysics

基　　金：supported by grants from The National Natural Science Foundation of China (30670654, 90919004)~~

摘　　要：为探讨兴奋性神经传递系统是否参与冷水应激引起的tau蛋白磷酸化,将小鼠于4℃冷水应激5min.采用免疫印迹和免疫组织化学方法分析应激后脑内c-fos和磷酸化tau蛋白的表达情况;运用HPLC检测冷水应激后小鼠脑内兴奋性或抑制性神经递质的变化;同时分析兴奋性氨基酸受体和L-型钙通道拮抗剂预处理后冷水应激小鼠脑内磷酸化tau蛋白的水平.冷水应激后1h,海马内磷酸化tau蛋白的水平显著升高,同时伴c-fos的染色增加.HPLC检测显示,兴奋性和抑制性神经递质呈现急剧上升而后又下降的趋势.冷水应激后15min,天冬氨酸和甘氨酸水平显著升高,1h后天冬氨酸、谷氨酸、牛磺酸和γ-氨基丁酸显著下降.NMDA受体拮抗剂MK-801(5mg/kg)和AMPA受体拮抗剂DNQX(0.5,5mg/kg)可显著抑制冷水应激引起的磷酸化tau蛋白水平的升高,代谢性谷氨酸受体拮抗剂MAP-4不影响tau蛋白的磷酸化,另外,L-型钙通道阻断剂尼莫地平可抑制冷水应激引起的磷酸化tau蛋白水平的升高.这些结果表明,冷水应激可影响兴奋性神经传递系统,通过离子型兴奋性氨基酸受体和异常神经激活来调节tau蛋白的磷酸化.兴奋性神经传递系统的激活在冷水应激诱导的海马tau蛋白的磷酸化中发挥作用.In order to investigate whether excitatory neurotransmission system takes roles in tau phosphorylation caused by cold water stress, mice were treated with cold water stress (CWS), which were forced to swim at 4℃ for 5 min. The tau phosphorylation in mice brains was analyzed by immunobloting and immunohistochemistry with c-fos and phosphorylation-dependent tau antibodies. To evaluate the imbalance of excitatory or inhibitory neurotransmitters system, HPLC was used to detect amino acid neurotransmitters in br...

关 键 词：冷水应激 TAU蛋白磷酸化 兴奋性氨基酸神经递质 HPLC 

分 类 号：Q42[生物学—神经生物学]