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Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence
HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly ad...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108358/ https://www.ncbi.nlm.nih.gov/pubmed/25054922 http://dx.doi.org/10.1371/journal.pone.0102555 |
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author | Desplats, Paula Dumaop, Wilmar Cronin, Peter Gianella, Sara Woods, Steven Letendre, Scott Smith, David Masliah, Eliezer Grant, Igor |
author_facet | Desplats, Paula Dumaop, Wilmar Cronin, Peter Gianella, Sara Woods, Steven Letendre, Scott Smith, David Masliah, Eliezer Grant, Igor |
author_sort | Desplats, Paula |
collection | PubMed |
description | HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive psychostimulant drug, abuse of which has reached epidemic proportions and is associated with high-risk sexual behavior, increased HIV transmission, and development of drug resistance. HIV infection and METH dependence can have synergistic pathological effects, with preferential involvement of frontostriatal circuits. At the molecular level, epigenetic alterations have been reported for both HIV-1 infection and drug abuse, but the neuropathological pathways triggered by their combined effects are less known. We investigated epigenetic changes in the brain associated with HIV and METH. We analyzed postmortem frontal cortex tissue from 27 HIV seropositive individuals, 13 of which had a history of METH dependence, in comparison to 14 cases who never used METH. We detected changes in the expression of DNMT1, at mRNA and protein levels, that resulted in the increase of global DNA methylation. Genome-wide profiling of DNA methylation in a subset of cases, showed differential methylation on genes related to neurodegeneration; dopamine metabolism and transport; and oxidative phosphorylation. We provide evidence for the synergy of HIV and METH dependence on the patterns of DNA methylation on the host brain, which results in a distinctive landscape for the comorbid condition. Importantly, we identified new epigenetic targets that might aid in understanding the aggravated neurodegenerative, cognitive, motor and behavioral symptoms observed in persons living with HIV and addictions. |
format | Online Article Text |
id | pubmed-4108358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41083582014-07-24 Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence Desplats, Paula Dumaop, Wilmar Cronin, Peter Gianella, Sara Woods, Steven Letendre, Scott Smith, David Masliah, Eliezer Grant, Igor PLoS One Research Article HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive psychostimulant drug, abuse of which has reached epidemic proportions and is associated with high-risk sexual behavior, increased HIV transmission, and development of drug resistance. HIV infection and METH dependence can have synergistic pathological effects, with preferential involvement of frontostriatal circuits. At the molecular level, epigenetic alterations have been reported for both HIV-1 infection and drug abuse, but the neuropathological pathways triggered by their combined effects are less known. We investigated epigenetic changes in the brain associated with HIV and METH. We analyzed postmortem frontal cortex tissue from 27 HIV seropositive individuals, 13 of which had a history of METH dependence, in comparison to 14 cases who never used METH. We detected changes in the expression of DNMT1, at mRNA and protein levels, that resulted in the increase of global DNA methylation. Genome-wide profiling of DNA methylation in a subset of cases, showed differential methylation on genes related to neurodegeneration; dopamine metabolism and transport; and oxidative phosphorylation. We provide evidence for the synergy of HIV and METH dependence on the patterns of DNA methylation on the host brain, which results in a distinctive landscape for the comorbid condition. Importantly, we identified new epigenetic targets that might aid in understanding the aggravated neurodegenerative, cognitive, motor and behavioral symptoms observed in persons living with HIV and addictions. Public Library of Science 2014-07-23 /pmc/articles/PMC4108358/ /pubmed/25054922 http://dx.doi.org/10.1371/journal.pone.0102555 Text en © 2014 Desplats et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Desplats, Paula Dumaop, Wilmar Cronin, Peter Gianella, Sara Woods, Steven Letendre, Scott Smith, David Masliah, Eliezer Grant, Igor Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence |
title | Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence |
title_full | Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence |
title_fullStr | Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence |
title_full_unstemmed | Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence |
title_short | Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence |
title_sort | epigenetic alterations in the brain associated with hiv-1 infection and methamphetamine dependence |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108358/ https://www.ncbi.nlm.nih.gov/pubmed/25054922 http://dx.doi.org/10.1371/journal.pone.0102555 |
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