静脉麻醉与电量交互改善抑郁症电休克治疗后学习记忆的LTP/LTD平衡机制

项目名称： 静脉麻醉与电量交互改善抑郁症电休克治疗后学习记忆的LTP/LTD平衡机制

项目编号： No.81201053

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 罗洁

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 抑郁症发病率高，电休克治疗（ECT）对其快速高效，但同时引起学习记忆障碍。现代ECT需在麻醉下进行，以丙泊酚、氯胺酮为代表的静脉麻醉药能够改善其学习记忆损害。本项目组已发现丙泊酚与ECT治疗核心参数电量发生交互作用，可调整不同电量ECT的效应。我们设想辅用适量中枢靶点为谷氨酸系统的氯胺酮，通过改善主要效应于中枢GABA系统的丙泊酚的麻醉环境及其与ECT电量的交互效应，从而加强保护ECT后学习记忆功能；其可能由学习记忆的电生理基础- - 长时程增强（LTP）和抑制（LTD）效应的平衡介导。为此，本项目拟：建立抑郁大鼠模型，对其行两种麻醉药及不同电量ECT处理后的行为学、在体脑电生理、离体脑片突触可塑性电生理、单细胞离子通道功能检测；并结合显微成像及分子生物学等手段，探讨静脉麻醉与ECT电量的交互效应在改善抑郁症ECT后学习记忆中的作用及其机制，以期为优化临床治疗策略提供更为科学的依据。

中文关键词： 静脉麻醉；抑郁症；学习记忆；电惊厥疗法；突触可塑性

英文摘要： Electroconvulsive therapy (ECT) is rapidly effective to refractory depression, but induces learning and memory impairment. Intravenous anesthetics, including propofol and ketamine, can alleviate those impairment. We have found that propofol and stimulus intensities of ECT interact with each other to effect,both in the behavioral and molecular levels. Thus, we hypothesize that the additional usage of ketamine, which mainly effectively targets on the glutamic system in the CNS, may improve the anesthetic efficacy of propofol, which mainly effectively targets on the GABA system in the CNS, rectify the interaction with stimulus intensities of ECT, and enhance the protection to learning and memory after undergoing ECT. Those effects may be mediated through the NMDA pathway's electrophysiological effects, including long term potentiation (LTP) and long term depression (LTD). In this study, we aim to establish the rodent model of depression, investigate the in vivo and ex vivo electrophysiological parameters, function of ion channels, imaging and molecular parameters, so as to study the interaction of intravenous anesthesia and stimulus intensities in improving learning and memory after undergoing ECT in depressed rats and its mechanism, which may offer the optimization for clinical treatment and novel cue for further

英文关键词： intravenous anesthesia；depression；learning and memory；electroconvulsive therapy；synaptic plasticity