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Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models

Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into th...

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Autores principales: Mews, Philipp, Cunningham, Ashley M., Scarpa, Joseph, Ramakrishnan, Aarthi, Hicks, Emily M., Bolnick, Sarah, Garamszegi, Susanna, Shen, Li, Mash, Deborah C., Nestler, Eric J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916993/
https://www.ncbi.nlm.nih.gov/pubmed/36763659
http://dx.doi.org/10.1126/sciadv.add8946
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author Mews, Philipp
Cunningham, Ashley M.
Scarpa, Joseph
Ramakrishnan, Aarthi
Hicks, Emily M.
Bolnick, Sarah
Garamszegi, Susanna
Shen, Li
Mash, Deborah C.
Nestler, Eric J.
author_facet Mews, Philipp
Cunningham, Ashley M.
Scarpa, Joseph
Ramakrishnan, Aarthi
Hicks, Emily M.
Bolnick, Sarah
Garamszegi, Susanna
Shen, Li
Mash, Deborah C.
Nestler, Eric J.
author_sort Mews, Philipp
collection PubMed
description Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls. Weighted gene coexpression analyses identified CUD-specific gene networks enriched in ionotropic receptors and linked to lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity.
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spelling pubmed-99169932023-02-11 Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models Mews, Philipp Cunningham, Ashley M. Scarpa, Joseph Ramakrishnan, Aarthi Hicks, Emily M. Bolnick, Sarah Garamszegi, Susanna Shen, Li Mash, Deborah C. Nestler, Eric J. Sci Adv Neuroscience Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls. Weighted gene coexpression analyses identified CUD-specific gene networks enriched in ionotropic receptors and linked to lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity. American Association for the Advancement of Science 2023-02-10 /pmc/articles/PMC9916993/ /pubmed/36763659 http://dx.doi.org/10.1126/sciadv.add8946 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Neuroscience
Mews, Philipp
Cunningham, Ashley M.
Scarpa, Joseph
Ramakrishnan, Aarthi
Hicks, Emily M.
Bolnick, Sarah
Garamszegi, Susanna
Shen, Li
Mash, Deborah C.
Nestler, Eric J.
Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models
title Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models
title_full Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models
title_fullStr Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models
title_full_unstemmed Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models
title_short Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models
title_sort convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916993/
https://www.ncbi.nlm.nih.gov/pubmed/36763659
http://dx.doi.org/10.1126/sciadv.add8946
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