电休克影响抑郁模型大鼠认知功能的机制研究

Effect of electric shock on cognitive function in depression model rats and its mechanism

摘要:

目的  观察不同电量和不同时程电休克（ECT）对嗅球切除抑郁模型大鼠海马谷氨酸（Glu）浓度和Tau蛋白过度磷酸化的影响以及ECT后学习记忆能力的变化。方法  建立大鼠嗅球切除抑郁模型，采用随机单位组3×3析因设计：将每只大鼠视为1个单位，对每个单位2个处理因素，即电流因子（3水平：25、50和75 mA）和时程因子（3水平：3、6和9次ECT）的所有组合（共9组，n =8）。全部ECT结束24 h内开始Morris水迷宫实验，检测实验大鼠海马区的长时程增强作用，留取海马组织。高效液相色谱法测海马中Glu的含量，免疫印迹法检测p-AT8Ser202、GSK-3β1H8在海马中的表达。结果  ECT引发海马Glu浓度升高及Tau蛋白磷酸化加剧，同时学习记忆能力相应下降，ECT的电流和时程均可影响该过程，两者的作用是相加的；GSK-3β是该过程信号通路的关键蛋白。结论  ECT导致海马中Glu浓度升高，从而加剧海马Tau蛋白的磷酸化程度，导致学习记忆障碍。

Abstract:

To explore the effect of the electroconvulsive shock (ECT) of different electric current and different duration on the hyperphosphorylation of tau protein and the change of the learning-memory ability in depressed rats. Methods The depression rat model was established by removing olfactory bulbs. As the analysis of variance of factorial design, two intervention factors were set up which were the electric current groups (three levels: 25, 50 and 75 mA) and the duration groups (three levels: 3, 3 and 9 times electroconvulsive shock). Fifty-four adult depression model rats were randomly divided into 9 experimental groups (6 in each group). The morris water maze test started within 1 day after the course of electroconvulsive shock in order to evaluate learning-memory. The long-term potentiation was detected in the hippocampus of rats. The hippocampus was removed from rats within 1 day after the morris water maze test was finished. The content of glutamate in the hippocampus of rats was detected by the high performance liquid chromatography and the content of tau protein including p-AT8Ser202 and GSK-3β1H8 in the hippocampus of rats was determined by Western blot. Results The electroconvulsive shock of different electric current and of different duration significantly up-regulated the content of glutamate and accelerated the hyperphosphorylation of tau protein and impaired learning-memory in depressed rats, with the performance of extending the evasive latency time and shortening the space exploration time in the depression model rats. The changes were correlated with the electric current and the duration of time of the electroconvulsive shock. GSK-3β was the key protein in this signaling pathway. Conclusions The results indicate that the electroconvulsive shock induces the impairment of learning-memory ability and the hyperphosphorylation of tau protein in depressed rats through up-regulated content of glutamate.