TY - GEN
T1 - Human immunodeficiency virus-1 protein Tat and methamphetamine interactions
AU - Theodore, Shaji
AU - Stolberg, Stephanie
AU - Cass, Wayne A.
AU - Maragos, William F.
PY - 2006/8
Y1 - 2006/8
N2 - The human immunodeficiency virus-1 (HIV-1) affects the central nervous system (CNS) in ∼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-α 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-α.
AB - The human immunodeficiency virus-1 (HIV-1) affects the central nervous system (CNS) in ∼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-α 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-α.
KW - AIDS
KW - Cytokines
KW - Dopamine
KW - Drug abuse
KW - Glia
KW - Neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=33749550160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749550160&partnerID=8YFLogxK
U2 - 10.1196/annals.1369.018
DO - 10.1196/annals.1369.018
M3 - Conference contribution
C2 - 17105916
AN - SCOPUS:33749550160
SN - 1573316296
SN - 9781573316293
T3 - Annals of the New York Academy of Sciences
SP - 178
EP - 190
BT - Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity
ER -