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Prion infections cause neurodegeneration, which often goes along with oxidative stress. However, the cellular source of reactive oxygen species (ROS) and their pathogenetic significance are unclear. Here we analyzed the contribution of NOX2, a prominent NADPH oxidase, to prion diseases. We found that NOX2 is markedly upregulated in microglia within affected brain regions of patients with Creutzfeldt-Jakob disease (CJD). Similarly, NOX2 expression was upregulated in prion-inoculated mouse brains and in murine cerebellar organotypic cultured slices (COCS). We then removed microglia from COCS using a ganciclovir-dependent lineage ablation strategy. NOX2 became undetectable in ganciclovir-treated COCS, confirming its microglial origin. Upon challenge with prions, NOX2-deficient mice showed delayed onset of motor deficits and a modest, but significant prolongation of survival. Dihydroethidium assays demonstrated a conspicuous ROS burst at the terminal stage of disease in wild-type mice, but not in NOX2-ablated mice. Interestingly, the improved motor performance in NOX2 deficient mice was already measurable at earlier stages of the disease, between 13 and 16 weeks post-inoculation. We conclude that NOX2 is a major source of ROS in prion diseases and can affect prion pathogenesis.
Pubmed ID: 25502554 RIS Download
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Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
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View all literature mentionslaboratory mouse with name C57BL/6JBomTac from MGI.
View all literature mentionslaboratory mouse with name C57BL/6NTac from MGI.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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