Upregulation of Superoxide Dismutase 2 by Astrocytes in the SIV/Macaque Model of HIV-Associated Neurologic Disease
| Autor: | Lisa M. Mangus, Nazareno Paolocci, Carlo Colantuoni, Joseph L. Mankowski, Gizem Keceli, Yea Ji Jeong, Clarisse V. Solis, Suzanne E. Queen, Samuel A. Brill, Audrey C Knight, Michelle N. Sullivan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
AIDS Dementia Complex Simian Acquired Immunodeficiency Syndrome SOD2 medicine.disease_cause Macaque Pathology and Forensic Medicine Superoxide dismutase 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation biology.animal medicine Animals skin and connective tissue diseases Neuroinflammation 030304 developmental biology Neurons 0303 health sciences biology Glial fibrillary acidic protein Superoxide Dismutase Brain virus diseases Original Articles General Medicine Simian immunodeficiency virus Up-Regulation 3. Good health medicine.anatomical_structure Anti-Retroviral Agents Neurology Astrocytes Immunology cardiovascular system biology.protein Simian Immunodeficiency Virus Microglia Neurology (clinical) Macaca nemestrina 030217 neurology & neurosurgery Immunostaining Astrocyte |
| Zdroj: | J Neuropathol Exp Neurol |
| ISSN: | 1554-6578 0022-3069 |
| DOI: | 10.1093/jnen/nlaa084 |
| Popis: | 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 co-localized 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 delay the onset or reduce severity of HAND seen in ART-treated HIV-infected patients. |
| Databáze: | OpenAIRE |
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