title: Oxidative Stress Is Associated with Neuroinflammation in Animal Models of HIV-1 Tat Neurotoxicity.
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.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. jplouboutin@hotmail.com.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Louboutin
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. lokagrawal@gmail.com.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Agrawal
authors.affiliation: Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA. beverly.reyes@drexelmed.edu.
authors.forename: Beverly A S
authors.initials: BA
authors.lastname: Reyes
authors.affiliation: Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA. elisabeth.vanbockstaele@drexelmed.edu.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Van Bockstaele
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. David.Strayer@jefferson.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Strayer
keywords: HIV-1; SV40; Tat; antioxidant enzymes; astrocytes; brain; gene therapy; microglia; neuroinflammation; oxidative stress