HIV-1 Tat neurotoxicity in primary cultures of rat midbrain fetal neurons: changes in dopamine transporter binding and immunoreactivity.
HIV-1 neurotoxic proteins (Tat, gp120) are believed to play a major role in pathogenesis of dementia in a significant portion of the AIDS patient population. Dopaminergic systems appear to be particularly important in HIV-associated dementia. In the current studies, we determined that primary cell cultures prepared from the midbrain of 18-day-old rat fetuses are sensitive to Tat neurotoxicity and investigated the possible effects of Tat on DAT-specific ligand binding and DAT immunoreactivity in rat fetal midbrain cultures. We found that Tat neurotoxicity was associated with a significant decrease in [3H]WIN 35428 binding. Immunostaining of cell cultures with antibodies recognizing the C-end epitope of DAT did not reveal significant changes in DAT immunoreactivity. The results of this study implicate involvement of monoamine transmission systems in HIV-associated dementia.
Aksenova
Marina V
MV
Department of Psychology, Program in Behavioral Neuroscience, University of South Carolina, 1512 Pendleton St, Columbia, 29208, USA. aksenova@gwm.sc.edu
Silvers
Janelle M
JM
Aksenov
Michael Y
MY
Nath
Avindra
A
Ray
Philip D
PD
Mactutus
Charles F
CF
Booze
Rosemarie M
RM
D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D000939:Epitopes / Q000235:genetics; D005260:Female; D015696:Gene Products, tat / Q000633:toxicity*; D015497:HIV-1 / Q000737:chemistry*; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D054322:tat Gene Products, Human Immunodeficiency Virus
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D000939:Epitopes; D015696:Gene Products, tat; D009498:Neurotoxins; D054322:tat Gene Products, Human Immunodeficiency Virus; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D010751:Phosphopyruvate Hydratase; D003042:Cocaine