ERRα Knockout Promotes M2 Microglial Polarization and Inhibits Ferroptosis in Sepsis-Associated Brain Dysfunction.

ABSTRACT: Sepsis-associated brain dysfunction (SABD) is a critical neurological complication with high mortality, yet its pathogenesis remains poorly understood. This study investigated the role of estrogen-related receptor α (ERRα) in SABD pathogenesis using ERRα knockout (KO) mice and cecal ligation and puncture (CLP) models. We found that ERRα KO mice exhibited improved survival rates, milder neurological symptoms, reduced pro-inflammatory cytokine production (TNF-α, IL-1β), and increased anti-inflammatory cytokine (IL-10) levels compared to wild-type controls. Additionally, ERRα deficiency promoted microglial M2 polarization and attenuated ferroptosis, as evidenced by decreased iron accumulation, reduced lipid peroxidation, and normalized mitochondrial morphology. Mechanistically, these protecti

SUBMITTER: Jin J 

PROVIDER: S-EPMC12367961 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature