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

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 & 5 others David Blum, Rodrigo A. Cunha, Hélène Marie, Paula A. Pousinha, Luísa V. Lopes

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1-25
Number of pages25
JournalMolecular Psychiatry
DOIs
Publication statusAccepted/In press - Jun 27 2018

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Adenosine A2A Receptors
N-Methyl-D-Aspartate Receptors
Alzheimer Disease
Neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Temido-Ferreira, M., Ferreira, D. G., Batalha, V. L., Marques-Morgado, I., Coelho, J. E., Pereira, P., ... Lopes, L. V. (Accepted/In press). Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors. Molecular Psychiatry, 1-25. https://doi.org/10.1038/s41380-018-0110-9

Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors. / Temido-Ferreira, Mariana; Ferreira, Diana G.; Batalha, Vânia L.; 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 A.; Lopes, Luísa V.

In: Molecular Psychiatry, 27.06.2018, p. 1-25.

Research output: Contribution to journalArticle

Temido-Ferreira, M, Ferreira, DG, Batalha, VL, Marques-Morgado, I, Coelho, JE, Pereira, P, Gomes, R, Pinto, A, Carvalho, S, Canas, PM, Cuvelier, L, Buée-Scherrer, V, Faivre, E, Baqi, Y, Müller, CE, Pimentel, J, Schiffmann, SN, Buée, L, Bader, M, Outeiro, TF, Blum, D, Cunha, RA, Marie, H, Pousinha, PA & Lopes, LV 2018, 'Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors', Molecular Psychiatry, pp. 1-25. https://doi.org/10.1038/s41380-018-0110-9
Temido-Ferreira, Mariana ; Ferreira, Diana G. ; Batalha, Vânia L. ; 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 A. ; Lopes, Luísa V. / Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors. In: Molecular Psychiatry. 2018 ; pp. 1-25.
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AU - Pereira, Pedro

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AU - Canas, Paula M.

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AU - Müller, Christa E.

AU - Pimentel, José

AU - Schiffmann, Serge N.

AU - Buée, Luc

AU - Bader, Michael

AU - Outeiro, Tiago F.

AU - Blum, David

AU - Cunha, Rodrigo A.

AU - Marie, Hélène

AU - Pousinha, Paula A.

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