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

Efrain A. Ribeiro, Joseph R. Scarpa, Susanna P. Garamszegi, Andrew Kasarskis, Deborah C. Mash, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Article number5412
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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