Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors

Autor: Andreia Pinto, José Pimentel, Michael Bader, Rodrigo A. Cunha, Luísa V. Lopes, Rui Gomes, Christa E. Müller, Inês Marques-Morgado, Vânia L. Batalha, Joana E. Coelho, Pedro M. Pereira, Laetitia Cuvelier, Tiago F. Outeiro, Diana G. Ferreira, Younis Baqi, Paula A. Pousinha, David Blum, Emilie Faivre, Serge N. Schiffmann, Luc Buée, Hélène Marie, Sara Carvalho, Mariana Temido-Ferreira, Valérie Buée-Scherrer, Paula M. Canas
Přispěvatelé: Repositório da Universidade de Lisboa, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Department of Electrical Engineering, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire de Neurophysiologie, Université libre de Bruxelles (ULB), STMicroelectronics [Rousset] (ST-ROUSSET), Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Molecular Biology of Peptide Hormone Group (MDC), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Universidade Federal da Bahia (UFBA), Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Blum, David
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Aging
Adenosine
Receptor
Adenosine A2A
Receptor
Metabotropic Glutamate 5
Adenosine A2A receptor
Gating
Hippocampal formation
Biology
Biochemistry
Hippocampus
Receptors
N-Methyl-D-Aspartate
Article
Rats
Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Alzheimer Disease
Age related
mental disorders
Animals
Humans
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Cognitive decline
Molecular Biology
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
Spatial Memory
Neurons
Neurophysiologie
Metabotropic glutamate receptor 5
Long-Term Synaptic Depression
Sciences bio-médicales et agricoles
Blockade
Rats
Psychiatry and Mental health
030104 developmental biology
nervous system
Cardiovascular and Metabolic Diseases
NMDA receptor
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neuroscience
Biologie
030217 neurology & neurosurgery
Zdroj: Molecular Psychiatry
Molecular Psychiatry, Nature Publishing Group, 2018, ⟨10.1038/s41380-018-0110-9⟩
Molecular Psychiatry, 2018, ⟨10.1038/s41380-018-0110-9⟩
Molecular psychiatry, 25 (8
ISSN: 1359-4184
1476-5578
Popis: © 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/.
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.
MT-F is an FCT/PhD Fellow (IMM Lisbon BioMed PhD program; SFRH/BD/52228/2013); VLB, DGF and JEC were supported by a fellowship from Fundação para a Ciência e Tecnologia (FCT, Portugal); LVL is an Investigator FCT. TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Goettingen, Germany. RAC is supported by Maratona da Saúde, Santa Casa da Misericórdia and ERDF, through Centro 2020 (project CENTRO-01-0145-FEDER-000008:BrainHealth 2020), and through FCT (projects POCI-01-0145-FEDER-007440 and PTDC/NEU-NMC/4154/2016). DB, VBS, EF, and LB are supported by Région Hauts de France (PARTNAIRR COGNADORA), ANR (ADORATAU and SPREADTAU), LECMA/Alzheimer Forschung Initiative, Programs d’Investissements d’Avenir LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to AD), France Alzheimer/Fondation de France, the FHU VasCog research network (Lille, France), Fondation pour la Recherche Médicale, Fondation Plan Alzheimer, INSERM, CNRS, Université Lille 2, Lille Métropole Communauté Urbaine, FEDER, DN2M, LICEND, and CoEN. LVL and DB are supported by AAP Internationalization, Université de Lille. EF is supported by ANR and Université de Lille. We would like to thank the Lille Neurobank for providing human brain tissues. HM and PAP supported by ATIP/AVENIR program (Center National de la Recherche Scientifique—CNRS), by the Foundation Plan Alzheimer (Senior Innovative Grant 2010) and PP by the Fondation pour la Recherche Médicale (FRM post-doctoral fellowship). Funded by LISBOA-01-0145-FEDER-007391, project co-financed by FEDER, POR Lisboa 2020—Programa Operacional Regional de Lisboa, from PORTUGAL 2020 and by Fundação para a Ciência e a Tecnologia (PTDC/BIM-MEC/47778/2014).
Databáze: OpenAIRE
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