Cargando…

Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder

Metabolic and functional alterations of neurons in the dorsolateral prefrontal cortex (dlPFC) are thought to contribute to impulsivity, which is a hallmark of addictive behaviors that underlie compulsive drug seeking and taking in humans. To determine if there is a transcriptional signature in dlPFC...

Descripción completa

Detalles Bibliográficos
Autores principales: Ribeiro, Efrain A., Scarpa, Joseph R., Garamszegi, Susanna P., Kasarskis, Andrew, Mash, Deborah C., Nestler, Eric J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511210/
https://www.ncbi.nlm.nih.gov/pubmed/28710498
http://dx.doi.org/10.1038/s41598-017-05720-3
_version_ 1783250294975496192
author Ribeiro, Efrain A.
Scarpa, Joseph R.
Garamszegi, Susanna P.
Kasarskis, Andrew
Mash, Deborah C.
Nestler, Eric J.
author_facet Ribeiro, Efrain A.
Scarpa, Joseph R.
Garamszegi, Susanna P.
Kasarskis, Andrew
Mash, Deborah C.
Nestler, Eric J.
author_sort Ribeiro, Efrain A.
collection PubMed
description Metabolic and functional alterations of neurons in the dorsolateral prefrontal cortex (dlPFC) are thought to contribute to impulsivity, which is a hallmark of addictive behaviors that underlie compulsive drug seeking and taking in humans. To determine if there is a transcriptional signature in dlPFC neurons of humans with cocaine use disorder, we performed total RNA-sequencing on neuronal nuclei isolated from post-mortem dlPFC of cocaine addicts and healthy controls. Our results point toward a transcriptional mechanism whereby cocaine alters specific gene networks in dlPFC neurons. In particular, we identified an AP-1 regulated transcriptional network in dlPFC neurons associated with cocaine use disorder that contains several differentially expressed hub genes. Several of these hub genes are GWAS hits for traits that might involve dysfunction of brain reward circuitry (Body-Mass Index, Obesity) or dlPFC (Bipolar disorder, Schizophrenia). Further study is warranted to determine their potential pathophysiological role in cocaine addiction.
format Online
Article
Text
id pubmed-5511210
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-55112102017-07-17 Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder Ribeiro, Efrain A. Scarpa, Joseph R. Garamszegi, Susanna P. Kasarskis, Andrew Mash, Deborah C. Nestler, Eric J. Sci Rep Article Metabolic and functional alterations of neurons in the dorsolateral prefrontal cortex (dlPFC) are thought to contribute to impulsivity, which is a hallmark of addictive behaviors that underlie compulsive drug seeking and taking in humans. To determine if there is a transcriptional signature in dlPFC neurons of humans with cocaine use disorder, we performed total RNA-sequencing on neuronal nuclei isolated from post-mortem dlPFC of cocaine addicts and healthy controls. Our results point toward a transcriptional mechanism whereby cocaine alters specific gene networks in dlPFC neurons. In particular, we identified an AP-1 regulated transcriptional network in dlPFC neurons associated with cocaine use disorder that contains several differentially expressed hub genes. Several of these hub genes are GWAS hits for traits that might involve dysfunction of brain reward circuitry (Body-Mass Index, Obesity) or dlPFC (Bipolar disorder, Schizophrenia). Further study is warranted to determine their potential pathophysiological role in cocaine addiction. Nature Publishing Group UK 2017-07-14 /pmc/articles/PMC5511210/ /pubmed/28710498 http://dx.doi.org/10.1038/s41598-017-05720-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ribeiro, Efrain A.
Scarpa, Joseph R.
Garamszegi, Susanna P.
Kasarskis, Andrew
Mash, Deborah C.
Nestler, Eric J.
Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
title Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
title_full Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
title_fullStr Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
title_full_unstemmed Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
title_short Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
title_sort gene network dysregulation in dorsolateral prefrontal cortex neurons of humans with cocaine use disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511210/
https://www.ncbi.nlm.nih.gov/pubmed/28710498
http://dx.doi.org/10.1038/s41598-017-05720-3
work_keys_str_mv AT ribeiroefraina genenetworkdysregulationindorsolateralprefrontalcortexneuronsofhumanswithcocaineusedisorder
AT scarpajosephr genenetworkdysregulationindorsolateralprefrontalcortexneuronsofhumanswithcocaineusedisorder
AT garamszegisusannap genenetworkdysregulationindorsolateralprefrontalcortexneuronsofhumanswithcocaineusedisorder
AT kasarskisandrew genenetworkdysregulationindorsolateralprefrontalcortexneuronsofhumanswithcocaineusedisorder
AT mashdeborahc genenetworkdysregulationindorsolateralprefrontalcortexneuronsofhumanswithcocaineusedisorder
AT nestlerericj genenetworkdysregulationindorsolateralprefrontalcortexneuronsofhumanswithcocaineusedisorder