Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment
dc.contributor.author | Brocos Mosquera, Iria | |
dc.contributor.author | Miranda Azpiazu, Patricia | |
dc.contributor.author | Muguruza Millán, Carolina | |
dc.contributor.author | Corzo Monje, Virginia | |
dc.contributor.author | Morentin Campillo, Benito | |
dc.contributor.author | Meana Martínez, José Javier | |
dc.contributor.author | Callado Hernando, Luis Felipe | |
dc.contributor.author | Rivero Calera, Guadalupe | |
dc.date.accessioned | 2022-01-14T09:05:40Z | |
dc.date.available | 2022-01-14T09:05:40Z | |
dc.date.issued | 2021-12-20 | |
dc.identifier.citation | Translational Psychiatry 11(1) : (2021) // Article ID 643 | es_ES |
dc.identifier.issn | 2158-3188 | |
dc.identifier.uri | http://hdl.handle.net/10810/54985 | |
dc.description.abstract | [EN] Postsynaptic alpha(2A)-adrenoceptor density is enhanced in the dorsolateral prefrontal cortex (DLPFC) of antipsychotic-treated schizophrenia subjects. This alteration might be due to transcriptional activation, and could be regulated by epigenetic mechanisms such as histone posttranslational modifications (PTMs). The aim of this study was to evaluate ADRA2A and ADRA2C gene expression (codifying for alpha(2)-adrenoceptor subtypes), and permissive and repressive histone PTMs at gene promoter regions in the DLPFC of subjects with schizophrenia and matched controls (n = 24 pairs). We studied the effect of antipsychotic (AP) treatment in AP-free (n = 12) and AP-treated (n = 12) subgroups of schizophrenia subjects and in rats acutely and chronically treated with typical and atypical antipsychotics. ADRA2A mRNA expression was selectively upregulated in AP-treated schizophrenia subjects (+93%) whereas ADRA2C mRNA expression was upregulated in all schizophrenia subjects (+53%) regardless of antipsychotic treatment. Acute and chronic clozapine treatment in rats did not alter brain cortex Adra2a mRNA expression but increased Adra2c mRNA expression. Both ADRA2A and ADRA2C promoter regions showed epigenetic modification by histone methylation and acetylation in human DLPFC. The upregulation of ADRA2A expression in AP-treated schizophrenia subjects might be related to observed bivalent chromatin at ADRA2A promoter region in schizophrenia (depicted by increased permissive H3K4me3 and repressive H3K27me3) and could be triggered by the enhanced H4K16ac at ADRA2A promoter. In conclusion, epigenetic predisposition differentially modulated ADRA2A and ADRA2C mRNA expression in DLPFC of schizophrenia subjects. | es_ES |
dc.description.sponsorship | This work was supported by Spanish MINECO (grant SAF2013-48586-R) and Basque Government (grant IT1211/19). The authors would like to thank the staff members of the Basque Institute of Legal Medicine for their cooperation in the study. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2013-48586-R | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | dorsolateral prefrontal cortex | es_ES |
dc.subject | alpha(2)-adrenoceptor subtypes | es_ES |
dc.subject | restrictive epigenome | es_ES |
dc.subject | dna hypermethylation | es_ES |
dc.subject | postmortem interval | es_ES |
dc.subject | histone methylation | es_ES |
dc.subject | bipolar disorder | es_ES |
dc.subject | agonist binding | es_ES |
dc.subject | messenger-rna | es_ES |
dc.subject | polymorphisms | es_ES |
dc.title | Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s) 2021. 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41398-021-01762-4 | es_ES |
dc.identifier.doi | 10.1038/s41398-021-01762-4 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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