Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors
Year: 2018
Type: article
Abstract: 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 A 2A receptor (A 2A R) encoding gene— ADORA2A , and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A 2A R in age-related conditions. We report, for the first time, a significant overexpression of A 2A R in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A 2A R 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 Ca 2+ influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A 2A R blockade. This A 2A R/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity.
Source: Molecular Psychiatry
Authors: Mariana Temido-Ferreira, Diana G. Ferreira, Vânia L. Batalha, Inês Marques-Morgado, Joana E. Coelho, Pedro Pereira, Rui Gomes, Andreia Pinto, Sara Carvalho, Paula M. Canas, Laetitia Cuvelier, Valerie Buée-Scherrer, Emilie Faivre, Younis Baqi, Christa E. Müller, José Pimentel, Serge N. Schiffmann, Luc Buée, Michael Bader, Tiago F. Outeiro, David Blum, Rodrigo A. Cunha, Hélène Marie, Paula A. Pousinha, Luísa V. Lopes
Institutions: University of Lisbon, Instituto de Medicina Molecular João Lobo Antunes, Universidade do Porto, Universitätsmedizin Göttingen, Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103, Centro de Investigação Farmacológica e Inovação Medicamentosa, University of Göttingen, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Centro de Neurociências e Biologia Celular, University of Coimbra, Université Libre de Bruxelles, Inserm, Université de Lille, Centre Hospitalier Universitaire de Lille, LabEx DISTALZ, University of Bonn, Sultan Qaboos University, Max Delbrück Center, Charité - Universitätsmedizin Berlin, University of Lübeck, Max Planck Institute of Experimental Medicine, Universidade Nova de Lisboa, Newcastle University, Centre National de la Recherche Scientifique, Université Côte d'Azur, Contrôle de la Réponse Immune B et Lymphoproliférations, Institut de Pharmacologie Moléculaire et Cellulaire
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: Alzheimer Forschung Initiative, Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease, Université de Lille, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Ministerio de Economía y Competitividad, Fondation de France, Centre National de la Recherche Scientifique, Programa Operacional Regional do Centro, Fundação para a Ciência e a Tecnologia, European Regional Development Fund
Awards: G1169839259, G1225170990, G1516346500, G1590170550, G1644592135, G1763632427, G196013823, 50005 .: Instituto de Medicina Molecular - IMM, G2413454803, G2737160601, G274581676, G323769159, Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime, UID/NEU/04539 .: CNC.IBILI, G3828612186, G3840324753, G4724859719, G5224927334, G5258554520, G5485649731, G5677667711, G5731524857, G6276858265, BrainHealth 2020: Deteção Precoce, Neuro-modulação e Terapias Avançadas para Neuropatologias, G7965899483, G946021960
OpenAlex ID: W2811459126