ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1647329
The SAP130/Mincle axis was involved in sevoflurane-induced neuronal death and microglial activation in juvenile mice
Provisionally accepted
- The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Sevoflurane is widely used in pediatric anesthesia, has raised concerns regarding its neurotoxic effects on the developing brain for years. Studies have shown that sevoflurane can lead to neuronal cell death and neuroinflammation, which further contributes to sevoflurane neurotoxicity that manifests delirium or cognitive deficits. However, the molecular mechanism remained poorly understood. A factor of interests is Sin3A-associated protein 130 (SAP130), which can be released by dead or damaged cells and trigger sterile inflammation to exacerbate tissue damage by activating macrophage-inducible C-type lectin (Mincle) receptor. However, whether the SAP130/Mincle axis was involved in sevoflurane neurotoxicity remained unknown. Using a young murine sevoflurane exposure model and primary neuron-microglia co-culture system, we examined changes in neuronal cell death, microglial activation, cytokine production, levels of SAP130 and Mincle signaling-associated proteins after sevoflurane exposure. We then applied SAP130 neutralizing antibody and syk inhibitor piceatannol to assess the impact of inhibiting the Mincle pathway on microglial activation and sevoflurane neurotoxicity. The results demonstrated that sevoflurane exposure increased the number of dead neurons with SAP130 upregulation and induced microglial activation with cytokine production in the hippocampus. These changes occurred only in neuron-microglia co-culture system but not in neuron or microglia monoculture. Neutralizing SAP130 or pharmacologically inhibiting syk diminished microglial activation and neuronal cell death by suppressing the SAP130/Mincle signaling pathway. These findings suggest that the SAP130/Mincle axis plays a crucial role in neuronal death and microglial activation in sevoflurane neurotoxicity.Targeting the SAP130/Mincle axis emerges as a potential therapeutic strategy to mitigate the neurotoxic effects of sevoflurane.
Keywords: Microglia, Neuroinflammation, Neuron, SAP130, Mincle, sevoflurane
Received: 15 Jun 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Zhou, Chen, Zhang, Shu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Bin Shu, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Ying Chen, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.