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Antioxidants 2014, 3(2), 414-438; doi:10.3390/antiox3020414
Article

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

1,* , 1
, 2,†
, 2,†
 and 1
Received: 12 March 2014; in revised form: 18 April 2014 / Accepted: 5 May 2014 / Published: 16 May 2014
(This article belongs to the Special Issue Free Radicals and Antioxidants in Neuroinflammation)
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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 HIV-1; Tat; oxidative stress; brain; antioxidant enzymes; gene therapy; SV40; neuroinflammation; microglia; astrocytes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.

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