Reference : Phagocytosis‐related NADPH oxidase 2 subunit gp91phox contributes to neurodegeneratio...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/44069
Phagocytosis‐related NADPH oxidase 2 subunit gp91phox contributes to neurodegeneration after repeated systemic challenge with lipopolysaccharides
English
Shahraz, Anahita [University of Bonn > Institute of Reconstructive Neurobiology]
Wißfeld, Jannis [University of Bonn > Institute of Reconstructive Neurobiology]
Ginolhac, Aurélien mailto [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 mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Neumann, Harald [University of Bonn > Institute of Reconstructive Neurobiology]
28-Jul-2020
Glia
John Wiley & Sons
Yes (verified by ORBilu)
International
0894-1491
1098-1136
Hoboken
NY
[en] lipopolysaccharides ; microglia ; NADPH oxidase ; neurodegeneration ; neuroinflammation ; phagocytes ; radicals
[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.
DFG
Researchers
http://hdl.handle.net/10993/44069
10.1002/glia.23890
https://doi.org/10.1002/glia.23890
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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