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Title: Early synaptic deficits in the APP/PS1 mouse model of Alzheimer's disease involve neuronal adenosine A2A receptors
Authors: Silva, Sílvia Viana da 
Haberl, Matthias Georg
Zhang, Pei
Bethge, Philipp
Lemos, Cristina 
Gonçalves, Nélio 
Gorlewicz, Adam
Malezieux, Meryl
Gonçalves, Francisco Q. 
Grosjean, Noëlle
Blanchet, Christophe
Frick, Andreas
Nägerl, U Valentin
Cunha, Rodrigo A. 
Mulle, Christophe 
Issue Date: 17-Jun-2016
Publisher: Springer Nature
Project: Centre National de la Recherche Scientifique, the Fundac¸a˜o para a Cieˆncia e a Tecnologia, Santa Casa da Miserico´rdia, the Fondation France Alzheimer, the Agence Nationale de la Recherche (contract SynflAD), the Conseil Re´gional d’Aquitaine and the Labex Brain 
Serial title, monograph or event: Nature Communications
Volume: 7
Issue: 1
Abstract: Synaptic plasticity in the autoassociative network of recurrent connections among hippocampal CA3 pyramidal cells is thought to enable the storage of episodic memory. Impaired episodic memory is an early manifestation of cognitive deficits in Alzheimer's disease (AD). In the APP/PS1 mouse model of AD amyloidosis, we show that associative long-term synaptic potentiation (LTP) is abolished in CA3 pyramidal cells at an early stage. This is caused by activation of upregulated neuronal adenosine A2A receptors (A2AR) rather than by dysregulation of NMDAR signalling or altered dendritic spine morphology. Neutralization of A2AR by acute pharmacological inhibition, or downregulation driven by shRNA interference in a single postsynaptic neuron restore associative CA3 LTP. Accordingly, treatment with A2AR antagonists reverts one-trial memory deficits. These results provide mechanistic support to encourage testing the therapeutic efficacy of A2AR antagonists in early AD patients.
ISSN: 2041-1723
DOI: 10.1038/ncomms11915
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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