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.
Keywords: HIV-1; Tat; oxidative stress ; brain; antioxidant enzymes; gene therapy; SV40; neuroinflammation; microglia; astrocytes
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Louboutin, J.-P.; Agrawal, L.; Reyes, B.A.S.; Van Bockstaele, E.J.; Strayer, D.S. Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity. Antioxidants 2014, 3, 414-438.
Louboutin J-P, Agrawal L, Reyes BAS, Van Bockstaele EJ, Strayer DS. Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity. Antioxidants. 2014; 3(2):414-438.
Louboutin, Jean-Pierre; Agrawal, Lokesh; Reyes, Beverly A.S.; Van Bockstaele, Elisabeth J.; Strayer, David S. 2014. "Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity." Antioxidants 3, no. 2: 414-438.