Lookup NU author(s): Professor Tiago Outeiro
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© 2018 The Author(s) 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.
Author(s): Temido-Ferreira M, Ferreira DG, Batalha VL, Marques-Morgado I, Coelho JE, Pereira P, Gomes R, Pinto A, Carvalho S, Canas PM, Cuvelier L, Buee-Scherrer V, Faivre E, Baqi Y, Muller CE, Pimentel J, Schiffmann SN, Buee L, Bader M, Outeiro TF, Blum D, Cunha RA, Marie H, Pousinha PA, Lopes LV
Publication type: Article
Publication status: Published
Journal: Molecular Psychiatry
Pages: Epub ahead of print
Online publication date: 27/06/2018
Acceptance date: 14/05/2018
Date deposited: 09/07/2018
ISSN (print): 1359-4184
ISSN (electronic): 1476-5578
Publisher: Nature Publishing Group
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