Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity

• Main Authors: Jean-Pierre Louboutin (Author), Lokesh Agrawal (Author), Beverly A. S. Reyes (Author), Elisabeth J. Van Bockstaele (Author), David S. Strayer (Author)
• Format: Book
• Published: MDPI AG, 2014-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2076-3921; 10.3390/antiox3020414
• Keywords: HIV-1; Tat; oxidative stress; brain; antioxidant enzymes; gene therapy; SV40; neuroinflammation; microglia; astrocytes; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 3, Iss 2, Pp 414-438 (2014)

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.