Article (Scientific journals)
Phagocytosis‐related NADPH oxidase 2 subunit gp91phox contributes to neurodegeneration after repeated systemic challenge with lipopolysaccharides
Shahraz, Anahita; Wißfeld, Jannis; Ginolhac, Aurélien et al.
2020In Glia
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Keywords :
lipopolysaccharides; microglia; NADPH oxidase; neurodegeneration; neuroinflammation; phagocytes; radicals
Abstract :
[en] Repeated systemic challenge with lipopolysaccharides (LPS) can induce microglia activation and inflammatory neurodegeneration in the substantia nigra pars compacta region of mice. We now explored the role of mononuclear phagocytes associated nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX‐2) in inflammatory neurodegeneration. Cybb ‐deficient 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. Transcriptome analysis by RNA‐seq of total brain tissue indicated increased LPS‐induced upregulation of genes belonging to the reactive oxygen species and reactive nitrogen species production, complement and lysosome activation as well as apoptosis and necroptosis in WT compared to NOX‐2 KO mice. Validation of up‐regulated gene transcripts via qRT‐PCR confirmed that LPS‐challenged NOX‐2 KO mice expressed lower levels of the microglial phagocytosis‐related genes Nos2 , Cd68 , Aif1/Iba1 , Cyba , Itgam , and Fcer1g compared to WT mice at Day 5 after systemic inflammatory challenge, but no significant differences in the pro‐inflammatory genes Tnfα and Il1b as well as microglial IBA1 and CD68 intensities were observed between both genotypes. Furthermore, loss of tyrosine hydroxylase positive (TH+) and NeuN positive neurons in the substantia nigra pars compacta upon repeated systemic LPS application were attenuated in NOX‐2 KO mice. Thus, our data demonstrate that loss of dopaminergic neurons in the substantia nigra pars compacta after repeated systemic challenge with LPS is associated with a microglial phagocytosis‐related gene activation profile involving the NADPH oxidase subunit Cybb/gp91phox.
Research center :
ULHPC - University of Luxembourg: High Performance Computing
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Shahraz, Anahita;  University of Bonn > Institute of Reconstructive Neurobiology
Wißfeld, Jannis;  University of Bonn > Institute of Reconstructive Neurobiology
Ginolhac, Aurélien  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Matthews, Mona;  University of Bonn > Institute of Reconstructive Neurobiology
Sinkkonen, Lasse  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Neumann, Harald;  University of Bonn > Institute of Reconstructive Neurobiology
External co-authors :
yes
Language :
English
Title :
Phagocytosis‐related NADPH oxidase 2 subunit gp91phox contributes to neurodegeneration after repeated systemic challenge with lipopolysaccharides
Publication date :
28 July 2020
Journal title :
Glia
ISSN :
1098-1136
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Funders :
DFG - Deutsche Forschungsgemeinschaft [DE]
Available on ORBilu :
since 10 August 2020

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