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| Pàgina inicial > Articles > Articles publicats > Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence |
(Centro de Investigación Biomédica en Red de Enfermedades Raras) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Radboud University Medical Center. Department of Psychiatry) (Universitat de Barcelona. Institut de Biomedicina)
| Data: | 2015 |
| Resum: | 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. |
| Ajuts: | Ministerio de Economía y Competitividad SAF2012-33484 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR932 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009SGR14 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR878 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR1357 Ministerio de Ciencia e Innovación FIS2011-28820-C02-01 Ministerio de Ciencia e Innovación FIS2013-41144-P Instituto de Salud Carlos III PI13/1911 |
| Drets: | 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | Translational psychiatry, Vol. 5 (october 2015) , p. e667, ISSN 2158-3188 |
