ArticleNeuropsychiatric disease and treatment2025
The Impact of Esketamine on Depression: Targeting Oxidative Stress and Neuronal Apoptosis Through BDNF/TrkB/PI3K/AKT Pathway Activation.
Article in Neuropsychiatric disease and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Effects of Intravenous Subanesthetic-Dose Esketamine on Early Postoperative Pain in Elderly Patients Undergoing Thoracoscopic Lung Surgery: A Randomized Double-Blind Controlled Trial.Drug design, development and therapy · 2025Trial
- Sustained effectiveness and safety of esketamine for major depressive disorder: a target trial simulation of real-world data.Translational psychiatry · 2026Article
Corrections and comments
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Authors and funding
4 authors.
Funding
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Abstract
Background & Aims: Esketamine, a promising treatment for treatment-resistant depression, has shown potential advantages over traditional antidepressants. However, its mechanisms remain unclear. This study explores how esketamine alleviates depressive behaviors through activation of the BDNF/TrkB/PI3K/AKT signaling pathway. Methods: Using a Chronic Unpredictable Mild Stress (CUMS) rat model, behavioral assays (Sucrose Preference Test, Morris Water Maze Test) and histological analyses (HE and Nissl's staining) were performed. Esketamine (5 mg/kg) treatment was administered to evaluate its antidepressant effects, and the PI3K inhibitor, PI3K-IN-6, was used to investigate the role of the PI3K/AKT pathway in the underlying mechanism. Results: Esketamine treatment improved depressive behaviors, enhanced neuronal structure, and reduced apoptosis and oxidative stress. These effects were linked to the activation of the BDNF/TrkB/PI3K/AKT pathway. PI3K-IN-6 reversed the effects, confirming the pathway's involvement. Conclusion: Esketamine alleviates depressive behaviors by activating the BDNF/TrkB/PI3K/AKT signaling pathway, reducing oxidative stress and inhibiting neuronal apoptosis. These findings highlight the therapeutic potential of esketamine in treating depression, particularly in cases where traditional treatments fail.
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Registered trials
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