Preferential sensitivity of human dopaminergic neurons to gp120-induced oxidative damage.
The dopamine (DA)-rich midbrain is known to be a key target of human immunodeficiency virus (HIV)-1. Studies of simian immunodeficiency virus (SIV)-induced neuropathogenesis recently established that there is a major disruption within the nigrostriatal dopaminergic system characterized by marked depletion of dopaminergic neurons, microglial cell activation, and reactive astrocytes. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, experiments were performed to characterize the damage to dopaminergic neurons induced by HIV-1 gp120. Functional impairment was assessed by DA uptake, and neurotoxicity was measured by apoptosis and oxidative damage. Through the use of this mesencephalic neuronal/glial culture model, we were able to identify the relative sensitivity of dopaminergic neurons to gp120-induced damage, manifested as reduced function (decreased DA uptake), morphological changes, and reduced viability. We also showed that gp120-induced oxidative damage is involved in this neuropathogenic process.
Hu
Shuxian
S
Center for Infectious Diseases and Microbiology Translational Research, Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Sheng
Wen S
WS
Lokensgard
James R
JR
Peterson
Phillip K
PK
Rock
R Bryan
RB
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000473:pathology / Q000821:virology; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D017382:Reactive Oxygen Species; C514793:gp120 protein, Human immunodeficiency virus 1; D004298:Dopamine