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

Abstract 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...

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Autores principales:	Efrain A. Ribeiro, Joseph R. Scarpa, Susanna P. Garamszegi, Andrew Kasarskis, Deborah C. Mash, Eric J. Nestler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70e04ba251b14c45af07c028fa6a9619
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spelling	oai:doaj.org-article:70e04ba251b14c45af07c028fa6a96192021-12-02T12:32:00ZGene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder10.1038/s41598-017-05720-32045-2322https://doaj.org/article/70e04ba251b14c45af07c028fa6a96192017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05720-3https://doaj.org/toc/2045-2322Abstract 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.Efrain A. RibeiroJoseph R. ScarpaSusanna P. GaramszegiAndrew KasarskisDeborah C. MashEric J. NestlerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Efrain A. Ribeiro Joseph R. Scarpa Susanna P. Garamszegi Andrew Kasarskis Deborah C. Mash Eric J. Nestler Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
description	Abstract 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	article
author	Efrain A. Ribeiro Joseph R. Scarpa Susanna P. Garamszegi Andrew Kasarskis Deborah C. Mash Eric J. Nestler
author_facet	Efrain A. Ribeiro Joseph R. Scarpa Susanna P. Garamszegi Andrew Kasarskis Deborah C. Mash Eric J. Nestler
author_sort	Efrain A. Ribeiro
title	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_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_sort	gene network dysregulation in dorsolateral prefrontal cortex neurons of humans with cocaine use disorder
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/70e04ba251b14c45af07c028fa6a9619
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Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder

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