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Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse

The development of new therapeutic strategies for the treatment of complex brain disorders such as drug addiction is likely to be advanced by a more complete understanding of the underlying molecular pathophysiology. Although the study of postmortem human brain represents a unique resource in this r...

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Autores principales: Bannon, Michael J., Savonen, Candace L., Hartley, Zachary J., Johnson, Magen M., Schmidt, Carl J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319936/
https://www.ncbi.nlm.nih.gov/pubmed/25658879
http://dx.doi.org/10.1371/journal.pone.0117580
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author Bannon, Michael J.
Savonen, Candace L.
Hartley, Zachary J.
Johnson, Magen M.
Schmidt, Carl J.
author_facet Bannon, Michael J.
Savonen, Candace L.
Hartley, Zachary J.
Johnson, Magen M.
Schmidt, Carl J.
author_sort Bannon, Michael J.
collection PubMed
description The development of new therapeutic strategies for the treatment of complex brain disorders such as drug addiction is likely to be advanced by a more complete understanding of the underlying molecular pathophysiology. Although the study of postmortem human brain represents a unique resource in this regard, it can be challenging to disentangle the relative contribution of chronic pathological processes versus perimortem events to the observed changes in gene expression. To begin to unravel this issue, we analyzed by quantitative PCR the midbrain expression of numerous candidate genes previously associated with cocaine abuse. Data obtained from chronic cocaine abusers (and matched control subjects) dying of gunshot wounds were compared with a prior study of subjects with deaths directly attributable to cocaine abuse. Most of the genes studied (i.e., tyrosine hydroxylase, dopamine transporter, forkhead box A2, histone variant H3 family 3B, nuclear factor kappa B inhibitor alpha, growth arrest and DNA damage-inducible beta) were found to be differentially expressed in chronic cocaine abusers irrespective of immediate cause of death or perimortem levels of cocaine, suggesting that these may represent core pathophysiological changes arising with chronic drug abuse. On the other hand, chemokine C-C motif ligand 2 and jun proto-oncogene expression were unaffected in cocaine-abusing subjects dying of gunshot wounds, in contrast to the differential expression previously reported in cocaine-related fatalities. The possible influence of cause of death and other factors on the cocaine-responsiveness of these genes is discussed.
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spelling pubmed-43199362015-02-18 Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse Bannon, Michael J. Savonen, Candace L. Hartley, Zachary J. Johnson, Magen M. Schmidt, Carl J. PLoS One Research Article The development of new therapeutic strategies for the treatment of complex brain disorders such as drug addiction is likely to be advanced by a more complete understanding of the underlying molecular pathophysiology. Although the study of postmortem human brain represents a unique resource in this regard, it can be challenging to disentangle the relative contribution of chronic pathological processes versus perimortem events to the observed changes in gene expression. To begin to unravel this issue, we analyzed by quantitative PCR the midbrain expression of numerous candidate genes previously associated with cocaine abuse. Data obtained from chronic cocaine abusers (and matched control subjects) dying of gunshot wounds were compared with a prior study of subjects with deaths directly attributable to cocaine abuse. Most of the genes studied (i.e., tyrosine hydroxylase, dopamine transporter, forkhead box A2, histone variant H3 family 3B, nuclear factor kappa B inhibitor alpha, growth arrest and DNA damage-inducible beta) were found to be differentially expressed in chronic cocaine abusers irrespective of immediate cause of death or perimortem levels of cocaine, suggesting that these may represent core pathophysiological changes arising with chronic drug abuse. On the other hand, chemokine C-C motif ligand 2 and jun proto-oncogene expression were unaffected in cocaine-abusing subjects dying of gunshot wounds, in contrast to the differential expression previously reported in cocaine-related fatalities. The possible influence of cause of death and other factors on the cocaine-responsiveness of these genes is discussed. Public Library of Science 2015-02-06 /pmc/articles/PMC4319936/ /pubmed/25658879 http://dx.doi.org/10.1371/journal.pone.0117580 Text en © 2015 Bannon 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
Bannon, Michael J.
Savonen, Candace L.
Hartley, Zachary J.
Johnson, Magen M.
Schmidt, Carl J.
Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse
title Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse
title_full Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse
title_fullStr Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse
title_full_unstemmed Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse
title_short Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse
title_sort investigating the potential influence of cause of death and cocaine levels on the differential expression of genes associated with cocaine abuse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319936/
https://www.ncbi.nlm.nih.gov/pubmed/25658879
http://dx.doi.org/10.1371/journal.pone.0117580
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