Regulation of hippocampal neuronal apoptosis and autophagy in mice with sepsis-associated encephalopathy by immunity-related GTPase M1

Aims Sepsis-associated encephalopathy (SAE) is a common complication of severe sepsis. Our goal was to investigate the role of immunity-related GTPase M1 (IRGM1) in SAE and its underlying mechanism. Methods A mouse sepsis model was established by cecal ligation and perforation. SAE was diagnosed by behavior, electroencephalography, and somatosensory evoked potentials. Wild-type mice with SAE were treated with SB203580 to block the p38 mitogen-activated protein kinase (MAPK) signaling pathway. We assessed hippocampal histological changes and the expression of IRGM1, interferon-gamma (IFN-gamma), and p38 MAPK signaling pathway-related proteins. Results Immunity-related GTPase M1 and IFN-gamma levels increased in the hippocampus, with apoptosis, autophagy, and the p38 MAPK signaling pathway activated in neurons. Administration of SB203580 to mice with SAE reduced apoptosis and autophagy. Relative to wild-type mice with SAE, the general condition of Irgm1(-/-) mice with SAE was worsened, the p38 MAPK signaling pathway was inhibited, and neuronal apoptosis and autophagy were reduced. The absence of IRGM1 exacerbated SAE, with higher p38 MAPK signaling pathway activity and increased apoptosis and autophagy. Conclusions During SAE, IRGM1 can at least partially regulate apoptosis and autophagy in hippocampal neurons through the p38 MAPK signaling pathway.