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Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors

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Item Type:Article
Title:Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors
Creators Name:Temido-Ferreira, M., Ferreira, D.G., Batalha, V.L., Marques-Morgado, I., Coelho, J.E., Pereira, P., Gomes, R., Pinto, A., Carvalho, S., Canas, P.M., Cuvelier, L., Buée-Scherrer, V., Faivre, E., Baqi, Y., Müller, C.E., Pimentel, J., Schiffmann, S.N., Buée, L., Bader, M., Outeiro, T.F., Blum, D., Cunha, R.A., Marie, H., Pousinha, P.A. and Lopes, L.V.
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 Ca(2+) 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.
Keywords:Adenosine, Adenosine A2A Receptor, Aging, Alzheimer Disease, Cultured Cells, Hippocampus, Long-Term Synaptic Depression, Metabotropic Glutamate 5 Receptor, N-Methyl-D-Aspartate Receptors, Neurons, Spatial Memory, Sprague-Dawley Rats, Animals, Mice, Rats
Source:Molecular Psychiatry
Publisher:Nature Publishing Group
Page Range:1876-1900
Date:August 2020
Official Publication:https://doi.org/10.1038/s41380-018-0110-9
PubMed:View item in PubMed

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