Effect of antipsychotic drugs on group II metabotropic glutamate receptor expression and epigenetic control in postmortem brains of schizophrenia subjects
dc.contributor.author | De la Cuesta Barrutia, Jon | |
dc.contributor.author | Martínez Peula, Oihane | |
dc.contributor.author | Rivero Calera, Guadalupe ![]() | |
dc.contributor.author | Santas Martín, Jon Ander | |
dc.contributor.author | Munarriz Cuezva, Eva | |
dc.contributor.author | Brocos Mosquera, Iria | |
dc.contributor.author | Miranda Azpiazu, Patricia | |
dc.contributor.author | Díez Alarcia, Rebeca ![]() | |
dc.contributor.author | Morentin Campillo, Benito | |
dc.contributor.author | Honer, William G. | |
dc.contributor.author | Callado Hernando, Luis Felipe ![]() | |
dc.contributor.author | Erdozáin Fernández, Amaia Maite | |
dc.contributor.author | Ramos Miguel, Alfredo | |
dc.date.accessioned | 2024-05-13T16:33:30Z | |
dc.date.available | 2024-05-13T16:33:30Z | |
dc.date.issued | 2024-02 | |
dc.identifier.citation | Translational Psychiatry 14 : (2024) // Article ID 113 | es_ES |
dc.identifier.issn | 2158-3188 | |
dc.identifier.uri | http://hdl.handle.net/10810/67924 | |
dc.description.abstract | Antipsychotic-induced low availability of group II metabotropic glutamate receptors (including mGlu2R and mGlu3R) in brains of schizophrenia patients may explain the limited efficacy of mGlu2/3R ligands in clinical trials. Studies evaluating mGlu2/3R levels in well-designed, large postmortem brain cohorts are needed to address this issue. Postmortem samples from the dorsolateral prefrontal cortex of 96 schizophrenia subjects and matched controls were collected. Toxicological analyses identified cases who were (AP+) or were not (AP-) receiving antipsychotic treatment near the time of death. Protein and mRNA levels of mGlu2R and mGlu3R, as well as GRM2 and GRM3 promoter-attached histone posttranslational modifications, were quantified. Experimental animal models were used to compare with data obtained in human tissues. Compared to matched controls, schizophrenia cortical samples had lower mGlu2R protein amounts, regardless of antipsychotic medication. Downregulation of mGlu3R was observed in AP- schizophrenia subjects only. Greater predicted occupancy values of dopamine D2 and serotonin 5HT2A receptors correlated with higher density of mGlu3R, but not mGlu2R. Clozapine treatment and maternal immune activation in rodents mimicked the mGlu2R, but not mGlu3R regulation observed in schizophrenia brains. mGlu2R and mGlu3R mRNA levels, and the epigenetic control mechanisms did not parallel the alterations at the protein level, and in some groups correlated inversely. Insufficient cortical availability of mGlu2R and mGlu3R may be associated with schizophrenia. Antipsychotic treatment may normalize mGlu3R, but not mGlu2R protein levels. A model in which epigenetic feedback mechanisms controlling mGlu3R expression are activated to counterbalance mGluR loss of function is described. | es_ES |
dc.description.sponsorship | The study was supported by grants PID2022-137848OB-I00 (to AR-M) and RTI2018-094414-A-I00 (to AR-M and AME) from the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund (AEI/MCIU/ERDF), BIO22/ALZ/002 from EiTB-Maratoia/BIOEF (to LFC and AR-M) and IT1512/22 (to LFC) from the Basque Government. AR-M is a ‘Ramón y Cajal’ Researcher (grant RYC-2016-19282), and is a member of the ExoPsyCog Consortium, funded by the IKUR-Neurobiosciences Strategy (Basque Government). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2022-137848OB-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICU/RTI2018-094414-A-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/RYC-2016-19282 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.title | Effect of antipsychotic drugs on group II metabotropic glutamate receptor expression and epigenetic control in postmortem brains of schizophrenia subjects | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s) 2024. 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/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41398-024-02832-z | es_ES |
dc.identifier.doi | 10.1038/s41398-024-02832-z | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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Except where otherwise noted, this item's license is described as © The Author(s) 2024. 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/.