{"title":"Esketamine alleviates depressive-like behavior in neuropathic pain mice through the METTL3-GluA1 pathway.","authors":"Xiaoming Ji, Zhimin Huang, Chenming Zhou, Yu Wang, Dongliang Geng, Guoliang Zhang, Yunxiao Kang, Rui Cui, Jinyang Wang, Tianyun Zhang","doi":"10.1007/s10565-024-09975-1","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"38"},"PeriodicalIF":5.3000,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775062/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology and Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10565-024-09975-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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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.
期刊介绍：
Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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