Reactive oxygen species generated by glia are responsible for neuron death induced by human immunodeficiency virus-glycoprotein 120 in vitro

Human immunodeficiency virus infection is often followed by neurodegeneration, the cause of motor and cognitive impairment in some patients affected by acquired immunodeficiency. Several in vitro data indicate glycoprotein (gp) 120 as one of the substances responsible for the neurodegenerative event...

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Bibliographic Details
Published in:Neuroscience 2001-01, Vol.107 (1), p.51-58
Main Authors: Viviani, B, Corsini, E, Binaglia, M, Galli, C.L, Marinovich, M
Format: Article
Language:English
Subjects:
AIDS
AIDS Dementia Complex - metabolism
AIDS Dementia Complex - pathology
AIDS Dementia Complex - physiopathology
Animals
Animals, Newborn
Biological and medical sciences
Calcium - metabolism
Cell Death - drug effects
Cell Death - physiology
Cell Survival - drug effects
Cell Survival - physiology
Cells, Cultured
Central Nervous System - metabolism
Central Nervous System - physiopathology
Central Nervous System - virology
Coculture Techniques
cytokines
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
glycoprotein gp120
Hippocampus - drug effects
Hippocampus - metabolism
Hippocampus - virology
HIV Envelope Protein gp120 - metabolism
HIV Envelope Protein gp120 - toxicity
HIV-1 - metabolism
HIV-1 - pathogenicity
Human immunodeficiency virus
Humans
Interleukin 1^b
Interleukin-1 - antagonists & inhibitors
Interleukin-1 - metabolism
Microbiology
Nerve Degeneration - metabolism
Nerve Degeneration - physiopathology
Nerve Degeneration - virology
Neuroglia - drug effects
Neuroglia - metabolism
Neuroglia - virology
Neurons - drug effects
Neurons - metabolism
Neurons - virology
neuron–glia interactions
neurotoxicity
oxidative stress
Oxidative Stress - physiology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species - metabolism
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
RNA, Messenger - drug effects
RNA, Messenger - metabolism
Trolox
Virology
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Summary:Human immunodeficiency virus infection is often followed by neurodegeneration, the cause of motor and cognitive impairment in some patients affected by acquired immunodeficiency. Several in vitro data indicate glycoprotein (gp) 120 as one of the substances responsible for the neurodegenerative event that takes place only if non-neuronal cells (glial cells) are present. Our purpose was to investigate the molecular mechanisms through which glial cells could affect neuron viability after exposure to gp120 protein. We used a sandwich co-culture of primary hippocampal neurons and primary glial cells, where the two cell populations face each other but are separable. Exposure of 1-week-old rat hippocampal neurons in co-culture with glia to 600 pM gp120 protein resulted in the death of 30% of neurons after 6 days of treatment. A significant increase of intracellular calcium ([Ca 2+] i), evident 72 h after gp120 exposure (control 45.8±7.6 nM, gp120 176.5±43.6 nM), preceded neuron death. The gp120 protein affected neither the viability nor the morphology or [Ca 2+] i of glial cells. However, a significant amount of reactive oxygen species as well as of interleukin-1β was produced. Treatment of the co-culture with an antibody against interleukin-1β prevented neuron increase of [Ca 2+] i and cell death but not glial production of reactive oxygen species, whereas prior incubation of glial cells with Trolox, an antioxidant analog of vitamin E, down-regulated interleukin-1β expression and completely prevented neuron cell death. Our results indicate that reactive oxygen species produced in glial cells by gp120 exposure cause neurodegeneration by inducing the synthesis of interleukin-1β.
ISSN:0306-4522
1873-7544
DOI:10.1016/S0306-4522(01)00332-3