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Journal article
Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity
Antioxidants, v 3(2), pp 414-438
01 Jun 2014
PMID: 26784879
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
HIV-1 trans-acting protein Tat, an essential protein for viral replication, is a key mediator of neurotoxicity. If Tat oxidant injury and neurotoxicity have been described, consequent neuroinflammation is less understood. Rat caudate-putamens (CPs) were challenged with Tat, with or without prior rSV40-delivered superoxide dismutase or glutathione peroxidase. Tat injection caused oxidative stress. Administration of Tat in the CP induced an increase in numbers of Iba-1- and CD68-positive cells, as well as an infiltration of astrocytes. We also tested the effect of more protracted Tat exposure on neuroinflammation using an experimental model of chronic Tat exposure. SV(Tat): a recombinant SV40-derived gene transfer vector was inoculated into the rat CP, leading to chronic expression of Tat, oxidative stress, and ongoing apoptosis, mainly located in neurons. Intra-CP SV(Tat) injection induced an increase in microglia and astrocytes, suggesting that protracted Tat production increased neuroinflammation. SV(SOD1) or SV(GPx1) significantly reduced neuroinflammation following Tat administration into the CP. Thus, Tat-induced oxidative stress, CNS injury, neuron loss and inflammation may be mitigated by antioxidant gene delivery.
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Details
- Title
- Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity
- Creators
- Jean-Pierre Louboutin - Thomas Jefferson UniversityLokesh Agrawal - Thomas Jefferson UniversityBeverly A. S. Reyes - Thomas Jefferson UniversityElisabeth J. Van Bockstaele - Thomas Jefferson UniversityDavid S. Strayer - Thomas Jefferson University
- Publication Details
- Antioxidants, v 3(2), pp 414-438
- Publisher
- Mdpi
- Number of pages
- 25
- Grant note
- MH70287; MH69122; AH48244 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000215260700014
- Scopus ID
- 2-s2.0-85010577705
- Other Identifier
- 991019184824304721
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- Food Science & Technology