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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05720-3 |
| _version_ | 1818400413201727488 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T07:36:10Z |
| format | Article |
| id | doaj.art-70e04ba251b14c45af07c028fa6a9619 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T07:36:10Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-70e04ba251b14c45af07c028fa6a96192022-12-21T23:11:11ZengNature PortfolioScientific Reports2045-23222017-07-017111010.1038/s41598-017-05720-3Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use DisorderEfrain A. Ribeiro0Joseph R. Scarpa1Susanna P. Garamszegi2Andrew Kasarskis3Deborah C. Mash4Eric J. Nestler5Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount SinaiDepartment of Neurology, University of Miami Miller School of MedicineDepartment of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount SinaiDepartment of Neurology, University of Miami Miller School of MedicineFishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount SinaiAbstract 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.https://doi.org/10.1038/s41598-017-05720-3 |
| spellingShingle | 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 Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-017-05720-3 |
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