The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons

Neurotoxicity of human immunodeficiency virus-1 (HIV) includes synaptic simplification and neuronal apoptosis. However, the mechanisms of HIV-associated neurotoxicity remain unclear, thus precluding an effective treatment of the neurological complications. The present study was undertaken to charact...

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Veröffentlicht in:Neurotoxicity research Jg. 29; H. 4; S. 583 - 593
Hauptverfasser: Avdoshina, Valeria, Fields, Jerel Adam, Castellano, Paul, Dedoni, Simona, Palchik, Guillermo, Trejo, Margarita, Adame, Anthony, Rockenstein, Edward, Eugenin, Eliseo, Masliah, Eliezer, Mocchetti, Italo
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Springer US 01.05.2016
Schlagworte:
Adult
Animals
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cells, Cultured
Cohort Studies
Electron Microscope Tomography
Gene Expression Regulation - genetics
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
HIV Envelope Protein gp120 - genetics
HIV Envelope Protein gp120 - toxicity
HIV Infections - complications
HIV Infections - pathology
Humans
Mice
Mice, Transgenic
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Middle Aged
Mitochondria - pathology
Mitochondria - ultrastructure
Mitochondrial Dynamics
Neurobiology
Neurochemistry
Neurology
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Neurons - ultrastructure
Neurosciences
Neurotoxicity Syndromes - genetics
Neurotoxicity Syndromes - pathology
Original Article
Pharmacology/Toxicology
Rats
Smegmamorpha
Time Factors
Mitochondrial respiration
HIVE
Oxygen consumption
Tom 20
Gp120ADA
Fis-1
ISSN:1029-8428, 1476-3524
Online-Zugang:Volltext
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Zusammenfassung:Neurotoxicity of human immunodeficiency virus-1 (HIV) includes synaptic simplification and neuronal apoptosis. However, the mechanisms of HIV-associated neurotoxicity remain unclear, thus precluding an effective treatment of the neurological complications. The present study was undertaken to characterize novel mechanisms of HIV neurotoxicity that may explain how HIV subjects develop neuronal degeneration. Several neurodegenerative disorders are characterized by mitochondrial dysfunction; therefore, we hypothesized that HIV promotes mitochondrial damage. We first analyzed brains from HIV encephalitis (HIVE) by electron microscopy. Several sections of HIVE subjects contained enlarged and damaged mitochondria compared to brains from HIV subjects with no neurological complications. Similar pathologies were observed in mice overexpressing the HIV protein gp120, suggesting that this viral protein may be responsible for mitochondrial pathology found in HIVE. To gain more information about the cellular mechanisms of gp120 neurotoxicity, we exposed rat cortical neurons to gp120 and we determined cellular oxygen consumption rate, mitochondrial distribution, and trafficking. Our data show that gp120 evokes impairment in mitochondrial function and distribution. These data suggest that one of the mechanisms of HIV neurotoxicity includes altered mitochondrial dynamics in neurons.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1029-8428
1476-3524
DOI:10.1007/s12640-016-9608-6