【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。更多还原

【Abstract】 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 tau 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 Tau-1 site(r=-0.963, P<0.05), and not significant at pS214 site(r=0.705, P>0.05). Conclusions Forskolin can induce tau hyperphosphorylation and spatial memory retentive deficit within a certain period of time. The level of tau phosphorylation in hippocampus is somehow correlated with the spatial memory deficit in rats.更多还原