Sevoflurane augments neuroinflammation by regulating DUSP6 via YTHDF1 in postoperative cognitive dysfunction

Area of Science:

• Neuroscience
• Anesthesiology
• Molecular Biology

Background:

• Postoperative cognitive dysfunction (POCD) is a recognized complication following anesthesia during surgery.
• Sevoflurane, a common inhaled anesthetic, is implicated in triggering neuroinflammation that contributes to POCD.

Purpose of the Study:

• To elucidate the pathological mechanism by which sevoflurane induces neuroinflammation and contributes to POCD.
• To investigate the roles of YTHDF1 and DUSP6 in sevoflurane-induced neuroinflammation.

Main Methods:

• Established a neurocyte injury model using human neuroblastoma cell lines (SH-SY5Y, SK-N-SH) treated with sevoflurane.
• Assessed cell viability (MTT), reactive oxygen species (ROS), lactate dehydrogenase (LDH) release, inflammatory cytokines, apoptosis (flow cytometry), gene expression (qRT-PCR), and protein abundance (western blotting).
• Validated interactions between YTHDF1 and DUSP6 using RNA immunoprecipitation (RIP)-qPCR and methylated RIP (MeRIP)-qPCR assays.

Main Results:

• Sevoflurane exposure induced apoptosis, oxidative stress, and neuroinflammation while downregulating YTHDF1 and DUSP6 expression.
• Overexpression of YTHDF1 counteracted sevoflurane-induced neuroinflammation.
• DUSP6 overexpression alleviated sevoflurane-induced neuroinflammation by modulating the ERK1/2 signaling pathway, with YTHDF1 enhancing DUSP6 expression.

Conclusions:

• Sevoflurane stimulates neuroinflammation in an in vitro POCD model by regulating DUSP6 expression via YTHDF1.
• YTHDF1 plays a critical role in mediating sevoflurane-induced neuroinflammation through the DUSP6/ERK1/2 pathway.