Propofol prevents electroconvulsive-shock-induced memory impairment through regulation of hippocampal synaptic plasticity in a rat model of depression
Authors Luo J, Min S, Wei K, Cao J, Wang B, Li P, Dong J, Liu Y
Received 1 May 2014
Accepted for publication 9 June 2014
Published 23 September 2014 Volume 2014:10 Pages 1847—1859
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Jie Luo, Su Min, Ke Wei, Jun Cao, Bin Wang, Ping Li, Jun Dong, Yuanyuan Liu
Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keyword: electroconvulsive therapy, long-term potentiation, PSD-95, CREB
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]