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http://hdl.handle.net/10451/55389| Título: | Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors |
| Autor: | Temido Ferreira, Mariana Ferreira, Diana Batalha, Vânia Marques-Morgado, Inês Coelho, Joana E Pereira, Pedro Gomes, Rui Pinto, Andreia Carvalho, Sara Canas, Paula M. Cuvelier, Laetitia Buée-Scherrer, Valerie Faivre, Emilie Baqi, Younis Müller, Christa E. Pimentel, José Schiffmann, Serge N. Buée, Luc Bader, Michael Outeiro, Tiago F. Blum, David Cunha, Rodrigo A. Marie, Hélène Pousinha, Paula Lopes, Luísa V. |
| Data: | 2018 |
| Editora: | Springer Nature |
| Citação: | Mol Psychiatry. 2020 Aug;25(8):1876-1900 |
| Resumo: | Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca2+ influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity. |
| Descrição: | © The Author(s) 2018. This article is published with open access. Open Access 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/. |
| Peer review: | yes |
| URI: | http://hdl.handle.net/10451/55389 |
| DOI: | 10.1038/s41380-018-0110-9 |
| ISSN: | 1359-4184 |
| Versão do Editor: | https://www.nature.com/mp/ |
| Aparece nas colecções: | IMM - Artigos em Revistas Internacionais FM - Artigos em Revistas Internacionais |
Ficheiros deste registo:
| Ficheiro | Descrição | Tamanho | Formato | |
|---|---|---|---|---|
| Age_shift.pdf | 5,71 MB | Adobe PDF | Ver/Abrir |
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