Propofol prevents electroconvulsive-shock-induced memory impairment through regulation of hippocampal synaptic plasticity in a rat model of depression.
Propofol prevents electroconvulsive-shock-induced memory impairment through regulation of hippocampal synaptic plasticity in a rat model of depression.
复制标题
异丙酚通过调节抑郁症大鼠模型海马突触可塑性来预防电休克引起的记忆障碍
DOI：
10.2147/ndt.s67108
复制
发表时间：
2014
影响因子：
3.2
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Luo J;Min S;Wei K;Cao J;Wang B;Li P;Dong J;Liu Y
尽管电休克疗法（ECT）是一种快速有效的精神科治疗方法，但它会导致记忆障碍。出于安全目的，改良 ECT 需要麻醉。虽然传统上发现全身麻醉会产生遗忘效应，这是改良 ECT 的固有部分，但一些麻醉剂被发现可以防止 ECT 引起的认知障碍。然而，其机制仍不清楚。我们研究了异丙酚（2,6-二异丙基苯酚）对麻醉下接受电休克（ECS）（动物 ECT 类似物）的抑郁大鼠记忆的影响及其机制。采用慢性不可预测的温和应激在啮齿动物模型中重现抑郁症。大鼠在异丙酚或生理盐水麻醉下接受 ECS（或假 ECS）。在蔗糖偏好、旷场和莫里斯水迷宫测试中评估行为。使用电生理技术测量海马长时程增强（LTP）。使用蛋白质印迹法测定 PSD-95、CREB 和 p-CREB 蛋白表达。抑郁症导致记忆损伤，并下调 LTP、PSD-95、CREB 和 p-CREB； ECS 在抑郁大鼠中加剧了这些影响；异丙酚并不能逆转抑郁引起的变化，但当在改良的 ECS 中给药时，异丙酚可以改善记忆并逆转 LTP 和蛋白质的下调。这些发现表明，异丙酚可以预防 ECS 引起的记忆损伤，并且在异丙酚麻醉下改良 ECS 可以改善抑郁大鼠的记忆力，这可能是通过逆转海马突触可塑性的过度变化来实现的。这些观察结果为优化 ECT 治疗精神疾病的临床应用的潜在目标提供了新的见解。
Although a rapid and efficient psychiatric treatment, electroconvulsive therapy (ECT) induces memory impairment. Modified ECT requires anesthesia for safety purposes. Although traditionally found to exert amnesic effects in general anesthesia, which is an inherent part of modified ECT, some anesthetics have been found to protect against ECT-induced cognitive impairment. However, the mechanisms remain unclear. We investigated the effects of propofol (2,6-diisopropylphenol) on memory in depressed rats undergoing electroconvulsive shock (ECS), the analog of ECT in animals, under anesthesia as well as its mechanisms. Chronic unpredictable mild stresses were adopted to reproduce depression in a rodent model. Rats underwent ECS (or sham ECS) with anesthesia with propofol or normal saline. Behavior was assessed in sucrose preference, open field and Morris water maze tests. Hippocampal long-term potentiation (LTP) was measured using electrophysiological techniques. PSD-95, CREB, and p-CREB protein expression was assayed with Western blotting. Depression induced memory damage, and downregulated LTP, PSD-95, CREB, and p-CREB; these effects were exacerbated in depressed rats by ECS; propofol did not reverse the depression-induced changes, but when administered in modified ECS, propofol improved memory and reversed the downregulation of LTP and the proteins. These findings suggest that propofol prevents ECS-induced memory impairment, and modified ECS under anesthesia with propofol improves memory in depressed rats, possibly by reversing the excessive changes in hippocampal synaptic plasticity. These observations provide a novel insight into potential targets for optimizing the clinical use of ECT for psychiatric disorders.