Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex.
Tian-Yuan Wang, H. Weng, Hong-Jin Zhou, Ze-Cheng Yang, Zhongyou Tian, Biao Xi, Yalan Li
Journal of Affective Disorders April 1, 2022 DOI: 10.1016/j.jad.2022.03.072 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Animal model of postoperative depression |
| Intervention | Esketamine |
| Topics | Depression Esketamine |
| Key findings | Esketamine improved depression-like behaviors in an animal model of postoperative depression and reversed inflammation-related reductions in parvalbumin neuron density and synaptogenesis in the medial prefrontal cortex. The authors suggest these anti-inflammatory effects may be mediated by BDNF/TrkB signaling and possibly by attenuation of the NF-κB pathway. |
Abstract
The rising incidence of Postoperative depression (POD) in recent years has placed a heavy burden on patients' physical and mental health. At this point in time, however, POD pathogenesis remains poorly understood and novel therapeutic strategies are being sought. The present study aimed to clarify esketamine's protective effects and possible mechanisms of action in POD. To this avail, we used an animal model of postoperative depression to analyze behavioral, parameters, plus the inflammatory response in serum and in the medial prefrontal cortex (mPFC). Using immunofluorescence staining, we detected the number of microglia and parvalbumin (PV) in mPFC, and determined changes in neuronal dendritic spine density via Golgi staining. Expression of Iba1, PSD95 and NF-κB was examined by Western blot analysis. Our results show that esketamine can significantly improve depression-like symptoms caused by anesthesia and surgery. In addition, esketamine administration reversed the decrease in the density of PV neurons and restored synaptogenesis in mPFC which had been perturbed by inflammation. The evidence obtained suggests esketamine's anti-inflammatory effects may be mediated by the BDNF/TrkB signaling pathway and possibly by attenuation of the nuclear factor κB (NF-κB) pathway. These data warrant further investigations into the interplay of esketamine, and microglia in the modulation of POD symptomatology.
Comparable studies
Other preclinical and animal studies on esketamine for depression, most cited first.
Citations in the library
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- The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics. Neurochemical Research April 1, 2023
- Optimizing esketamine administration for postoperative depression: a comprehensive study on laparoscopic bariatric surgery patients. Psychopharmacology February 1, 2025
- Esketamine improves cognitive function in sepsis-associated encephalopathy by inhibiting microglia-mediated neuroinflammation. European Journal of Pharmacology November 15, 2024
- Effects of esketamine and fluoxetine on depression-like behaviors in chronic variable stress: a role of plasma inflammatory factors. Frontiers in Psychiatry 2024
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Cites 12
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochemical Pharmacology July 1, 2020
- Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study Drug Design, Development and Therapy December 1, 2019
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