Transcriptional signatures in prefrontal cortex confer vulnerability versus resilience to food and cocaine addiction-like behavior

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  • dc.contributor.author Navandar, Mohit
  • dc.contributor.author Martín García, Elena, 1975-
  • dc.contributor.author Maldonado, Rafael, 1961-
  • dc.contributor.author Lutz, Beat
  • dc.contributor.author Gerber, Susanne
  • dc.contributor.author Ruiz de Azua, Iñigo
  • dc.date.accessioned 2021-06-09T07:37:31Z
  • dc.date.available 2021-06-09T07:37:31Z
  • dc.date.issued 2021
  • dc.description.abstract Addiction is a chronic relapsing brain disease characterized by compulsive reward-seeking despite harmful consequences. The mechanisms underlying addiction are orchestrated by transcriptional reprogramming in the reward system of vulnerable subjects. This study aims at revealing gene expression alterations across different types of addiction. We analyzed publicly available transcriptome datasets of the prefrontal cortex (PFC) from a palatable food and a cocaine addiction study. We found 56 common genes upregulated in the PFC of addicted mice in these two studies, whereas most of the differentially expressed genes were exclusively linked to either palatable food or cocaine addiction. Gene ontology analysis of shared genes revealed that these genes contribute to learning and memory, dopaminergic synaptic transmission, and histone phosphorylation. Network analysis of shared genes revealed a protein-protein interaction node among the G protein-coupled receptors (Drd2, Drd1, Adora2a, Gpr6, Gpr88) and downstream targets of the cAMP signaling pathway (Ppp1rb1, Rgs9, Pde10a) as a core network in addiction. Upon extending the analysis to a cell-type specific level, some of these common molecular players were selectively expressed in excitatory neurons, oligodendrocytes, and endothelial cells. Overall, computational analysis of publicly available whole transcriptome datasets provides new insights into the molecular basis of addiction-like behaviors in PFC.
  • dc.description.sponsorship We thank the financial support of the Spanish “Ministerio de Ciencia, Innovación y Universidades” (#AEI-SAF2017-84060-R FEDER), the “Instituto de Salud Carlos III” (#RD16/0017/0020), the “Plan Nacional Sobre Drogas” of the Spanish “Ministerio de Sanidad, Servicios Sociales e Igualdad” (#RD16/0017/0020 & #PNSD-2017I068) and the AGAUR of the “Generalitat de Catalunya” (#2017-SGR-669 and #ICREA-Acadèmia 2015) to R.M. and Fundació La Marató-TV3 (#2016/20-30) and Plan Nacional Sobre Drogas (#PNSD-2019I006) to E.M.G.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Navandar M, Martín-García E, Maldonado R, Lutz B, Gerber S, Ruiz de Azua I. Transcriptional signatures in prefrontal cortex confer vulnerability versus resilience to food and cocaine addiction-like behavior. Sci Rep. 2021;11(1):9076. DOI: 10.1038/s41598-021-88363-9
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-021-88363-9
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/47810
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Sci Rep. 2021;11(1):9076
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2017-84060-R
  • dc.rights © The Author(s) 2021. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Addiction
  • dc.subject.keyword Data processing
  • dc.title Transcriptional signatures in prefrontal cortex confer vulnerability versus resilience to food and cocaine addiction-like behavior
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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