The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function

Detalhes bibliográficos
Autor(a) principal: Batalha, Vânia
Data de Publicação: 2016
Outros Autores: Ferreira, Diana, Coelho, Joana E, Valadas, Jorge S., Gomes, Rui, Temido Ferreira, Mariana, Shmidt, Tatiana, Baqi, Younis, Buée, Luc, Müller, Christa E., Hamdane, Malika, Outeiro, Tiago, Bader, Michael, Meijsing, Sebastiaan H., Sadri-Vakili, Ghazaleh, Blum, David, Lopes, Luisa V.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/55394
Resumo: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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spelling The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer's and age-related cognitive impairments may rely on its ability to modulate GR actions.VLB and DGF were supported by a grant from Fundação para a Ciência e Tecnologia and an EMBO fellowship (Harvard Medical School-GSV lab- exchange period); LVL is an Investigator FCT, funded by Fundação para a Ciência e Tecnologia (PTDC-099853/2009). TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain. MH, LB and DB thank the following supports: LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer’s disease), Inserm, CNRS, Université Lille 2, Région Nord/Pas-de-Calais, DN2M, ANR (ADORATAU) and FUI MEDIALZ. DB, CEM and YB are grateful for support by the LECMA/Alzheimer Forschung Initiative (AFI). DB and LVL were recipients of PHC FCT/Pessoa program and are currently recipients of an international exchange program (AAP Internationalisation / LIA) funded by the University of Lille.Springer NatureRepositório da Universidade de LisboaBatalha, VâniaFerreira, DianaCoelho, Joana EValadas, Jorge S.Gomes, RuiTemido Ferreira, MarianaShmidt, TatianaBaqi, YounisBuée, LucMüller, Christa E.Hamdane, MalikaOuteiro, TiagoBader, MichaelMeijsing, Sebastiaan H.Sadri-Vakili, GhazalehBlum, DavidLopes, Luisa V.2022-12-14T14:05:27Z20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55394engSci Rep. 2016 Aug 11;6:31493.10.1038/srep314932045-2322info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:02:20Zoai:repositorio.ul.pt:10451/55394Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:02.933872Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
title The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
spellingShingle The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
Batalha, Vânia
title_short The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
title_full The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
title_fullStr The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
title_full_unstemmed The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
title_sort The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
author Batalha, Vânia
author_facet Batalha, Vânia
Ferreira, Diana
Coelho, Joana E
Valadas, Jorge S.
Gomes, Rui
Temido Ferreira, Mariana
Shmidt, Tatiana
Baqi, Younis
Buée, Luc
Müller, Christa E.
Hamdane, Malika
Outeiro, Tiago
Bader, Michael
Meijsing, Sebastiaan H.
Sadri-Vakili, Ghazaleh
Blum, David
Lopes, Luisa V.
author_role author
author2 Ferreira, Diana
Coelho, Joana E
Valadas, Jorge S.
Gomes, Rui
Temido Ferreira, Mariana
Shmidt, Tatiana
Baqi, Younis
Buée, Luc
Müller, Christa E.
Hamdane, Malika
Outeiro, Tiago
Bader, Michael
Meijsing, Sebastiaan H.
Sadri-Vakili, Ghazaleh
Blum, David
Lopes, Luisa V.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Batalha, Vânia
Ferreira, Diana
Coelho, Joana E
Valadas, Jorge S.
Gomes, Rui
Temido Ferreira, Mariana
Shmidt, Tatiana
Baqi, Younis
Buée, Luc
Müller, Christa E.
Hamdane, Malika
Outeiro, Tiago
Bader, Michael
Meijsing, Sebastiaan H.
Sadri-Vakili, Ghazaleh
Blum, David
Lopes, Luisa V.
description © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-01-01T00:00:00Z
2022-12-14T14:05:27Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/55394
url http://hdl.handle.net/10451/55394
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Sci Rep. 2016 Aug 11;6:31493.
10.1038/srep31493
2045-2322
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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