dc.contributor.author |
Fernández-Castillo, Noelia |
dc.contributor.author |
Cabana-Domínguez, Judit |
dc.contributor.author |
Soriano, J. |
dc.contributor.author |
Sànchez-Mora, C. |
dc.contributor.author |
Roncero, Carlos |
dc.contributor.author |
Grau-López, Lara |
dc.contributor.author |
Ros-Cucurull, E. |
dc.contributor.author |
Daigre, Constanza |
dc.contributor.author |
van Donkelaar, M. M. J. |
dc.contributor.author |
Franke, Barbara |
dc.contributor.author |
Casas, M. |
dc.contributor.author |
Ribasés, M.. |
dc.contributor.author |
Cormand, Bru |
dc.date |
2015 |
dc.identifier |
https://ddd.uab.cat/record/185458 |
dc.identifier |
urn:10.1038/tp.2015.158 |
dc.identifier |
urn:oai:ddd.uab.cat:185458 |
dc.identifier |
urn:pmid:26506053 |
dc.identifier |
urn:pmcid:PMC4930134 |
dc.identifier |
urn:pmc-uid:4930134 |
dc.identifier |
urn:articleid:21583188v5e667 |
dc.identifier |
urn:scopus_id:84989332535 |
dc.identifier |
urn:wos_id:000367665000004 |
dc.identifier |
urn:altmetric_id:4682140 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/4b6067ff-26f0-4197-8282-4357c5961efc |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:4930134 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Ministerio de Economía y Competitividad SAF2012-33484 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR932 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2009SGR14 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR878 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR1357 |
dc.relation |
Ministerio de Ciencia e Innovación FIS2011-28820-C02-01 |
dc.relation |
Ministerio de Ciencia e Innovación FIS2013-41144-P |
dc.relation |
Instituto de Salud Carlos III PI13/1911 |
dc.relation |
Translational psychiatry ; Vol. 5 (october 2015), p. e667 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.title |
Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence |
dc.type |
Article |
dc.description.abstract |
Cocaine reward and reinforcing effects are mediated mainly by dopaminergic neurotransmission. In this study, we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y-differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression changes and a concomitant increase in neuronal activity were observed after a 5 μ cocaine exposure, whereas no changes in gene expression or in neuronal activity took place at 1 μ cocaine. Changes in gene expression were identified in a total of 756 genes, mainly related to regulation of transcription and gene expression, cell cycle, adhesion and cell projection, as well as mitogen-activeated protein kinase (MAPK), CREB, neurotrophin and neuregulin signaling pathways. Some genes displaying altered expression were subsequently targeted with predicted functional single-nucleotide polymorphisms (SNPs) in a case-control association study in a sample of 806 cocaine-dependent patients and 817 controls. This study highlighted associations between cocaine dependence and five SNPs predicted to alter microRNA binding at the 3'-untranslated region of the NFAT5 gene. The association of SNP rs1437134 with cocaine dependence survived the Bonferroni correction for multiple testing. A functional effect was confirmed for this variant by a luciferase reporter assay, with lower expression observed for the rs1437134G allele, which was more pronounced in the presence of hsa-miR-509. However, brain volumes in regions of relevance to addiction, as assessed with magnetic resonance imaging, did not correlate with NFAT5 variation. These results suggest that the NFAT5 gene, which is upregulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence. |