The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons.
Title | The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Avdoshina, V, Fields, JAdam, Castellano, P, Dedoni, S, Palchik, G, Trejo, M, Adame, A, Rockenstein, E, Eugenin, E, Masliah, E, Mocchetti, I |
Journal | Neurotox Res |
Volume | 29 |
Issue | 4 |
Pagination | 583-593 |
Date Published | 2016 May |
ISSN | 1476-3524 |
Keywords | Adult, Animals, Cells, Cultured, Cohort Studies, Electron Microscope Tomography, Gene Expression Regulation, Green Fluorescent Proteins, HIV Envelope Protein gp120, HIV Infections, Humans, Mice, Mice, Transgenic, Microtubule-Associated Proteins, Middle Aged, Mitochondria, Mitochondrial Dynamics, Neurons, Neurotoxicity Syndromes, Rats, Smegmamorpha, Time Factors |
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. |
DOI | 10.1007/s12640-016-9608-6 |
Alternate Journal | Neurotox Res |
PubMed ID | 26936603 |
PubMed Central ID | PMC4821687 |
Grant List | P30AI087714 / AI / NIAID NIH HHS / United States P30 AI087714 / AI / NIAID NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States R01 MH096625 / MH / NIMH NIH HHS / United States R01 MH062962 / MH / NIMH NIH HHS / United States F32 NS083426 / NS / NINDS NIH HHS / United States R01 NS105584 / NS / NINDS NIH HHS / United States P30 AI117970 / AI / NIAID NIH HHS / United States AG043384 / AG / NIA NIH HHS / United States MH83506 / MH / NIMH NIH HHS / United States NS083426-01 / NS / NINDS NIH HHS / United States R21 NS104000 / NS / NINDS NIH HHS / United States NS074916 / NS / NINDS NIH HHS / United States R01 AG043384 / AG / NIA NIH HHS / United States MH062962 / MH / NIMH NIH HHS / United States R25 MH081482 / MH / NIMH NIH HHS / United States MH5974 / MH / NIMH NIH HHS / United States MH096625 / MH / NIMH NIH HHS / United States R01 NS040670 / NS / NINDS NIH HHS / United States NS079172 / NS / NINDS NIH HHS / United States R01 NS079172 / NS / NINDS NIH HHS / United States U01 MH083506 / MH / NIMH NIH HHS / United States R21 NS074916 / NS / NINDS NIH HHS / United States |