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 via PubMed
Summary
AI-generated from the abstractEsketamine, a new antidepressant, reduces depressive-like behavior in mice with neuropathic pain by boosting levels of the m6A methyltransferase METTL3 and the AMPA receptor GluA1 subunit. Esketamine activates METTL3, which binds to GluA1 mRNA and promotes m6A modification, enhancing GluA1 expression at synapses. This mechanism offers new insights into esketamine's potential applications and therapeutic avenues for neuropathic pain and depressive behavior.
Study at a glance
| 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 |
| Citations | 6 |
| Key finding | 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.