大鼠侧脑室单次注射Forskolin引起tau蛋白异常磷酸化和记忆障碍持续时间及其两者的关系  

Duration of tau Hyperphosphorylation and Spatial Memory Deficit Induced by Single Injection of Forskolin into Lateral Ventricle of Rat

作　　者：张军霞[1] 王玥[1] 田青[1] 朱铃强[1] 王建枝[1] 

机构地区：[1]华中科技大学同济医学院病理生理学系,武汉430030

出　　处：《中国医学科学院学报》2006年第3期355-359,i0003,共6页Acta Academiae Medicinae Sinicae

基　　金：国家重点基础性研究项目(2006CB500703);国家自然科学基金(30400068;30400171;30430270)~~

摘　　要：目的探讨侧脑室单次注射Forskolin后,大鼠海马组织中tau蛋白异常磷酸化和记忆障碍持续时间及两者关系。方法向大鼠侧脑室内单次注射80μmol/L的cAMP-依赖性蛋白激酶A(PKA)激动剂-Forskolin40μl,用特定抗体通过免疫印迹和免疫组织化学方法检测大鼠海马tau蛋白磷酸化水平的改变,同时用Morris水迷宫法检测大鼠空间记忆能力。结果侧脑室注射Forskolin后,大鼠海马tau蛋白磷酸化水平在24、48和72h均有显著升高(P<0·05),在48h达到高峰(P<0·01),在72h呈恢复趋势;大鼠在注射后24、48和72h均有空间记忆障碍(P<0·05),这种记忆障碍在48h最明显(P<0·01),在72h时亦呈明显恢复趋势;大鼠空间记忆保留障碍与海马tau蛋白PHF-1位点的磷酸化程度呈正相关(r=0·97,P<0·05),与Tau-1位点的非磷酸化程度呈负相关(r=-0·963,P<0·05),与pS214位点的磷酸化程度无相关性(r=0·705,P>0·05)。结论大鼠侧脑室单次注射Forskolin只在一定时间内引起tau蛋白异常磷酸化和动物记忆障碍,且二者的改变趋势存在一定相关性。Objective To investigate the duration of tau hyperphosphorylation and spatial memory retentive deficit induced by single injecting with Forskolin, a protein kinase A activator, into lateral ventricle of rats, and the correlation between the two pathological alterations. Methods Forskolin （80 μmoL/L, 40 μl） was injected into the lateral ventricle by stereotaxic injection. Tau phosphorylation and spatial memory retention were measured by Western blot/immunocytochemistry and Morris-Water-Maze test, respectively. Results The phosphorylation levels of tan at Tau-1, PHF-1, and pS214 epitopes were significantly elevated at 24, 48 and 72 h after single administration of Forskolin （ P 〈 0. 05 ）. The most significant elevation was seen at 48 h （P 〈 0. 01 ） and it tended to recover at 72 h （ P 〈 0. 05 ） after injection. The correlation between the two pathological alterations was positive at PHF-1 site （r =0.97, P 〈0.05）, negative at Tan-1 site （r= -0.963, P 〈0.05）, and not significant at pS214 site （r =0. 705, P 〉0. 05）. Condusions Forskolin can induce tan hyperphosphorylation and spatial memory retentive deficit within a certain period of time. The level of tan phosphorylation in hippocampus is somehow correlated with the spatial memory deficit in rats.

关 键 词：cAMP-依赖性蛋白激酶A TAU蛋白 磷酸化 空间记忆 阿尔茨海默病 

分 类 号：R745.7[医药卫生—神经病学与精神病学] Q513[医药卫生—临床医学]