Temporal relationships between HIV-1 Tat-induced neuronal degeneration, OX-42 immunoreactivity, reactive astrocytosis, and protein oxidation in the rat striatum.
HIV-1 transactivating protein Tat is neurotoxic and is believed to play a role in the development of AIDS-associated dementia complex. Neurotoxicity of Tat may be associated with oxidative stress. In this study we examined temporal progression of histopathological changes induced by a single microinjection of Tat 1-72 into the rat striatum. Degenerating neural cells, detected by Fluoro-Jade B staining and increased protein oxidation, determined by protein carbonyl immunostaining, were observed in the striatum as soon as 2 h following the microinjection. Further progression of neuronal degeneration was associated with pronounced infiltration of the area surrounding Tat 1-72 injection site by OX-42 positive macrophages/microglia, which was evident at the 24 h time point. Signs of reactive astrocytosis were found in the striatum of Tat 1-72 injected animals as late as 7 days following the single microinjection. Increased GFAP immunoreactivity and changes in the morphology of astrocytes coincided with a second phase of increased protein carbonyl formation, but not with neuronal degeneration. Control polypeptide, nontoxic Tat delta 31-61, did not cause any cell death, inflammatory reaction or oxidative damage. Results of our study support the hypothesis that oxidative stress may be an early step in the mechanism of Tat neurotoxicity.
D000123:Acetyltransferases / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D003342:Corpus Striatum / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism / Q000821:virology*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D051548:Histone Acetyltransferases; D015151:Immunoblotting; D007150:Immunohistochemistry; D000074443:Lysine Acetyltransferase 5; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D008562:Membrane Glycoproteins; D051926:Basigin; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5