Esketamine alleviates neuroinflammation and cognitive impairment in male 3xTg-AD mice by regulating the TAOK1/IL-17 axis.
Ting Xu, Chao Zhang, Yang Yang, Ziyi Shen, Zhangzhen Zhong
Canadian journal of physiology and pharmacology January 1, 2026 DOI: 10.1139/cjpp-2025-0340 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal and cell study Peer reviewed |
|---|---|
| Population | 3xTg-AD male mice and mouse cortical neurons |
| Interventions | Esketamine adeno-associated virus mouse IL-17A protein TAOK1 knockdown IL-17RA knockdown |
| Topics | Esketamine |
| Keywords | Alzheimer's disease Il-17 Taok1 Neuroinflammation |
| Key points | Esketamine protected against DNA damage-mediated neuroinflammation and improved cognitive dysfunction in 3xTg-AD mice, acting in a TAOK1-dependent manner by promoting TAOK1 and inhibiting IL-17 signaling. TAOK1 interacted with IL-17RA, and IL-17RA knockdown likewise reduced DNA damage and inflammation in cells and alleviated cognitive impairment and neuroinflammation in the mice. |
Abstract
Beyond its antidepressant effects, esketamine (ESK) has the potential to enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes, improving social cognition, and promoting resilience. However, not much is known about its role in Alzheimer's disease (AD). This study aims to explore the potential mechanism of ESK in AD treatment. The potential targets of ESK were predicted by bioinformatics analysis, and 3xTg-AD male mice were subjected to adeno-associated virus and ESK treatment. Cognitive ability, neuronal damage, and proinflammatory factors in 3xTg-AD mice were evaluated. An inflammatory model was established by inducing mouse cortical neurons with mouse IL-17A protein. Neuronal viability was assessed after treatment with different concentrations of ESK. TAOK1 knockdown or IL-17RA knockdown was performed on 3xTg-AD mice and neurons. TAOK1 was highly expressed in the cerebral cortex of ESK-treated 3xTg-AD mice. ESK improved IL-17-induced neuronal inflammation and DNA damage in a TAOK1-dependent manner. TAOK1 interacted with IL-17RA. IL-17RA knockdown improved DNA damage and inflammatory responses in cells and alleviated cognitive impairment and neuroinflammation in AD mice. Overall, ESK protects against DNA damage-mediated neuroinflammation by promoting TAOK1 and inhibiting IL-17 signaling, thereby improving cognitive dysfunction in 3xTg-AD mice.
Comparable studies
Other preclinical and animal studies on esketamine, most cited first.
Citations in the library
Cites 9
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- Esketamine Prevents Postoperative Emotional and Cognitive Dysfunction by Suppressing Microglial M1 Polarization and Regulating the BDNF-TrkB Pathway in Ageing Rats with Preoperative Sleep Disturbance Molecular Neurobiology January 15, 2024
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Esketamine vs. placebo combined with erector spinae plane block vs. intercostal nerve block on quality of recovery following thoracoscopic lung resection: a randomized controlled factorial trial. International Journal of Surgery 2025
- Esketamine improves cognitive function in sepsis-associated encephalopathy by inhibiting microglia-mediated neuroinflammation. European Journal of Pharmacology November 15, 2024
and 4 more in the library