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
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Abstract	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.
AbstractList	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.
Author	Adame, Anthony Masliah, Eliezer Fields, Jerel Adam Rockenstein, Edward Eugenin, Eliseo Avdoshina, Valeria Castellano, Paul Dedoni, Simona Trejo, Margarita Mocchetti, Italo Palchik, Guillermo
AuthorAffiliation	3 Department of Microbiology and Molecular Genetics, Public Health Research Institute Center and at the International Center for Public Health New Jersey Medical School - Rutgers, The State University of New Jersey, Newark, NJ, USA 4 Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA 1 Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 2 Department of Pathology, University of California San Diego, La Jolla, CA, USA 5 Department of Neurosciences, University of California San Diego, La Jolla, CA, USA
AuthorAffiliation_xml	– name: 4 Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA – name: 3 Department of Microbiology and Molecular Genetics, Public Health Research Institute Center and at the International Center for Public Health New Jersey Medical School - Rutgers, The State University of New Jersey, Newark, NJ, USA – name: 1 Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA – name: 5 Department of Neurosciences, University of California San Diego, La Jolla, CA, USA – name: 2 Department of Pathology, University of California San Diego, La Jolla, CA, USA
Author_xml	– sequence: 1 givenname: Valeria surname: Avdoshina fullname: Avdoshina, Valeria organization: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center – sequence: 2 givenname: Jerel Adam surname: Fields fullname: Fields, Jerel Adam organization: Department of Pathology, University of California San Diego – sequence: 3 givenname: Paul surname: Castellano fullname: Castellano, Paul organization: Department of Microbiology and Molecular Genetics, Public Health Research Institute Center and at the International Center for Public Health New Jersey Medical School - Rutgers, The State University of New Jersey – sequence: 4 givenname: Simona surname: Dedoni fullname: Dedoni, Simona organization: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center – sequence: 5 givenname: Guillermo surname: Palchik fullname: Palchik, Guillermo organization: Department of Radiation Oncology, University of Texas Southwestern Medical Center – sequence: 6 givenname: Margarita surname: Trejo fullname: Trejo, Margarita organization: Department of Pathology, University of California San Diego – sequence: 7 givenname: Anthony surname: Adame fullname: Adame, Anthony organization: Department of Pathology, University of California San Diego – sequence: 8 givenname: Edward surname: Rockenstein fullname: Rockenstein, Edward organization: Department of Pathology, University of California San Diego – sequence: 9 givenname: Eliseo surname: Eugenin fullname: Eugenin, Eliseo organization: Department of Microbiology and Molecular Genetics, Public Health Research Institute Center and at the International Center for Public Health New Jersey Medical School - Rutgers, The State University of New Jersey – sequence: 10 givenname: Eliezer surname: Masliah fullname: Masliah, Eliezer organization: Department of Pathology, University of California San Diego, Department of Neurosciences, University of California San Diego – sequence: 11 givenname: Italo surname: Mocchetti fullname: Mocchetti, Italo email: moccheti@georgetown.edu organization: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center
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Snippet	Neurotoxicity of human immunodeficiency virus-1 (HIV) includes synaptic simplification and neuronal apoptosis. However, the mechanisms of HIV-associated...
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SubjectTerms	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
Title	The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons
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