HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures.
HIV-1-associated cognitive/motor dysfunction is a frequent neurological complication of acquired immunodeficiency syndrome (AIDS) and has been termed AIDS dementia complex (ADC). The HIV-1 envelope glycoprotein gp120 has been implicated in producing brain injury associated with ADC. The purpose of the present study was to determine if gp120-induced neurotoxicity is associated with damage to dopaminergic systems. Exposure of rat midbrain dopamine cultures to gp120 for 3 days reduced the ability of dopaminergic cells to transport this amine and also resulted in a reduction in dopamine neuron process length while it did not alter either dopamine cell number or the total number of neuronal cells. These detrimental effects of gp120 were prevented by an NMDA receptor antagonist (MK-801) or by preincubation with anti-gp120 antibody. These results suggest that dopaminergic neuronal damage may contribute to the manifestations of AIDS dementia complex.
Bennett
B A
BA
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1083, USA.
Rusyniak
D E
DE
Hollingsworth
C K
CK
D000818:Animals; D000918:Antibody Specificity; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology / Q000821:virology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D014316:Tritium; D004298:Dopamine