Electroconvulsive therapy combined with esketamine improved depression through PI3K/AKT/GLT-1 pathway.

Autor: Zang X; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China., Zhang J; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China., Hu J; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China., Mo X; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China., Zheng T; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China., Ji J; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China., Xing J; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China. Electronic address: xingjb3@mail2.sysu.edu.cn., Chen C; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China. Electronic address: chenchj28@mail.sysu.edu.cn., Zhou S; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China. Electronic address: zhshli@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2025 Jan 01; Vol. 368, pp. 282-294. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1016/j.jad.2024.08.123
Abstrakt: Neuron excitotoxic damage induced by extracellular glutamate accumulation pathologically is one of the main mechanisms of depression. Glutamate transporter-1 (GLT-1) expressed in astrocyte is responsible for glutamate clearance to maintain glutamate balance. Electroconvulsive therapy (ECT) is prevalently recommended for severe depression due to its significant anti-depressant effect. Esketamine could offer advantages of rapid anti-depressant effect and neuron protection. The aim of this study is to investigate the anti-depressant efficacy of esketamine plus ECT, and further to explore the mechanism. Firstly, total 12 patients were randomized into anesthesia with propofol (P) or propofol+esketamine (PK) before ECT. 24-Hamilton Depression Scale (HAMD) was used to evaluate the severity of depression after each ECT. Then, depressive rat model was built using chronic unpredictable mild stress method, and subsequently received infusion of esketamine (5 mg/kg) or saline before ECT treatment (0.5 mA; 100 V) for consecutive 10 days. Tests including sucrose preference test, open field test and forced swimming test were used to evaluate depression-like behaviors. In next experiments, rats were injected with RIL, DHK or LY294002 intracerebroventricularly for continuous 10 days before individual treatment. After the fifth and sixth ECT, PK group displayed lower HAMD score compared to P group. In rat model, we found that esketamine plus ECT could significantly improve depression-like behaviors and decrease glutamate level. Esketamine and ECT could both activate PI3K/Akt/GLT-1 pathway. The GLT-1 agonist RIL made equivalent effect as esketamine plus ECT. Furthermore, after using PI3K/Akt inhibitor LY294002 and GLT-1 inhibitor DHK, esketamine plus ECT could neither improve depression-like symptoms, nor upregulate GLT-1 level. Our present study suggested that esketamine plus ECT could dramatically improve depression symptom. The activation of PI3K/Akt/GLT-1 pathway may be the potential mechanism.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chaojin Chen reports financial support was provided by Guangzhou Association for Science and Technology. Chaojin Chen reports financial support was provided by Third Affiliated Hospital of Sun Yat-Sen University. Shaoli Zhou reports financial support was provided by Guangdong Pharmaceutical Association Foundation. Chaojin Chen reports financial support was provided by Guangdong Province-Regional Innovation Capacity and Support System Construction. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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