Esketamine alleviates depressive-like behavior in neuropathic pain mice through the METTL3-GluA1 pathway.
Xiaoming Ji, Zhimin Huang, Chenming Zhou, Yu Wang, Dongliang Geng, Guoliang Zhang, Yunxiao Kang, Rui Cui, Jinyang Wang, Tianyun Zhang
Cell Biology and Toxicology January 29, 2025 DOI: 10.1007/s10565-024-09975-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo study with transcriptome sequencing and bioinformatics analysis Peer reviewed |
|---|---|
| Population | Neuropathic pain mice |
| Intervention | Esketamine |
| Topics | Esketamine |
| Keywords | Depressive behavior M6a methyltransferase mettl3 Neuropathic pain Pain-management Neuroscience-research Antidepressant-therapy Molecular-biology Psychiatric-medicine |
| Citations | 6 |
| Key points | Esketamine reduces depressive-like behavior in neuropathic pain mice by activating METTL3 to enhance GluA1 expression via m6A modification. |
Abstract
Esketamine, a newly developed antidepressant, is the subject of this research which seeks to explore its impact on depressive symptoms in neuropathic pain mice and the potential molecular mechanisms involved. Through transcriptome sequencing and bioinformatics analysis combined with in vivo studies, it was identified that esketamine markedly boosts the levels of the m6A methyltransferase METTL3 and the AMPA receptor GluA1 subunit. Esketamine activates METTL3, allowing it to bind with GluA1 mRNA, promoting m6A modification, thereby enhancing GluA1 expression at synapses. Through this mechanism, esketamine may reduce depressive-like behavior in neuropathic pain mice, providing new insights into the potential applications of esketamine and novel therapeutic avenues for neuropathic pain and depressive behavior.
Comparable studies
Other preclinical and animal studies on esketamine, most cited first.
Citations in the library
Cited by 4
- Esketamine alleviates the pain-depression dyad: insights from exploratory transcriptomic profiling and Wnt4-associated molecular alterations within the anterior cingulate cortex Frontiers in Pharmacology October 16, 2026
- Multiband ALFF in patients with major depressive disorder treated with esketamine and sertraline: A preliminary study Brain Research Bulletin October 6, 2026
- Ascorbic acid enhances antidepressant-like efficacy of esketamine: Hippocampal TARP-γ8-containing AMPA receptors mediate synaptic modulation. Neurotherapeutics November 11, 2025
- The epigenetic mechanisms of ketamine in the treatment of depression: a systematic review. Epigenomics November 7, 2025
Cites 12
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder American Journal of Psychiatry January 11, 2022
- Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability. The Lancet Psychiatry November 1, 2022
- Ketamine treatment for depression: a review Discover Mental Health April 15, 2022
- Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants Translational Psychiatry September 20, 2016
and 7 more in the library