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Upregulation of Superoxide Dismutase 2 by Astrocytes in the SIV/Macaque Model of HIV-Associated Neurologic Disease.
- Source :
-
Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2020 Sep 01; Vol. 79 (9), pp. 986-997. - Publication Year :
- 2020
-
Abstract
- HIV-associated neurocognitive disorders (HAND) remain prevalent despite implementation of antiretroviral therapy (ART). Development of HAND is linked to mitochondrial dysfunction and oxidative stress in the brain; therefore, upregulation of antioxidant defenses is critical to curtail neuronal damage. Superoxide dismutase 2 (SOD2) is a mitochondrial antioxidant enzyme essential for maintaining cellular viability. We hypothesized that SOD2 was upregulated during retroviral infection. Using a simian immunodeficiency virus (SIV)-infected macaque model of HIV, quantitative PCR showed elevated SOD2 mRNA in cortical gray ([GM], 7.6-fold for SIV vs uninfected) and white matter ([WM], 77-fold for SIV vs uninfected) during SIV infection. Further, SOD2 immunostaining was enhanced in GM and WM from SIV-infected animals. Double immunofluorescence labeling illustrated that SOD2 primarily colocalized with astrocyte marker glial fibrillary acidic protein (GFAP) in SIV-infected animals. Interestingly, in ART-treated SIV-infected animals, brain SOD2 RNA levels were similar to uninfected animals. Additionally, using principal component analysis in a transcriptomic approach, SOD2 and GFAP expression separated SIV-infected from uninfected brain tissue. Projection of these data into a HIV dataset revealed similar expression changes, thereby validating the clinical relevance. Together, our findings suggest that novel SOD2-enhancing therapies may reduce neuroinflammation in ART-treated HIV-infected patients.<br /> (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)
- Subjects :
- Animals
Anti-Retroviral Agents pharmacology
Brain enzymology
Macaca nemestrina
Male
Microglia enzymology
Neurons enzymology
Simian Acquired Immunodeficiency Syndrome complications
Simian Immunodeficiency Virus
Superoxide Dismutase drug effects
Up-Regulation
AIDS Dementia Complex enzymology
Astrocytes enzymology
Simian Acquired Immunodeficiency Syndrome enzymology
Superoxide Dismutase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-6578
- Volume :
- 79
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of neuropathology and experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 32783052
- Full Text :
- https://doi.org/10.1093/jnen/nlaa084