Human immunodeficiency virus-1 protein tat and methamphetamine interactions.
The human immunodeficiency virus-1 (HIV-1) affects the central nervous system (CNS) in approximately 30% of infected individuals and basal ganglia structures seem to be most affected. The HIV-1-transactivating protein, Tat, has been suggested to be pathogenically relevant in HIV-1-induced neuronal injury. The abuse of methamphetamine (METH), which is great among this patient population, also affects the basal ganglia, causing degeneration of dopaminergic terminals. In previous studies, we demonstrated that coexposure to these two toxins caused a synergistic loss of striatal dopamine and binding to the dopamine transporter (DAT), suggesting a loss of dopamine terminals. Because the loss of dopamine and DAT, however, do not necessarily reflect dopamine terminal degeneration, we have used silver staining and TH immunohistochemistry to further examine this issue. We have also examined the glial reaction using GFAP as a marker of astrocyte activation and OX-42 as a marker of activated microglia. Lastly, we have begun to explore the mechanism of synergy by investigating the role that the cytokine TNF-alpha might play in Tat + METH synergy. Our data indicate that the synergistic loss of dopamine is likely the result of dopamine terminal degeneration. This injury is not a direct result of the number of activated glia but does involve TNF-alpha.
Theodore
Shaji
S
Department of Neurology, University of Kentucky, 260 Health Science Research Building, 1095 V.A. Drive, Lexington, KY 40536-0305, USA.
Stolberg
Stephanie
S
Cass
Wayne A
WA
Maragos
William F
WF
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D015696:Gene Products, tat / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000187:drug effects; D051381:Rats; D016622:Silver Staining; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D015696:Gene Products, tat; D014409:Tumor Necrosis Factor-alpha; D008694:Methamphetamine; D004298:Dopamine