Phagocytosis-related NADPH oxidase 2 subunit gp91phox contributes to neurodegeneration after repeated systemic challenge with lipopolysaccharides

Here, we investigated the role of mononuclear phagocytes associated nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX-2) in inflammatory neurodegeneration. Cybb-deficient mice NOX-2 knock-out (KO) and control wild type (WT) mice were treated intraperitoneally daily over four consecutive days with 1 µg/gbw/day LPS. Repeated LPS injections led to inflammation and neuronal loss in the brains of WT mice, which was attenuated after knockout of NOX-2. Transcriptome analysis by RNA-seq of total brain tissue indicated increased LPS-induced upregulation of genes belonging to the reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, complement and lysosome activation as well as apoptosis and necroptosis in WT compared to NOX-2 KO mice. Overall design: Examination of brain mRNA profiles after repeated LPS or PBS (vehicle control) application of 3-month-old WT and NOX-2 KO mice by RNA-Seq (6 animals per group).