Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/108713
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Silva, Sílvia Viana da | - |
dc.contributor.author | Haberl, Matthias Georg | - |
dc.contributor.author | Zhang, Pei | - |
dc.contributor.author | Bethge, Philipp | - |
dc.contributor.author | Lemos, Cristina | - |
dc.contributor.author | Gonçalves, Nélio | - |
dc.contributor.author | Gorlewicz, Adam | - |
dc.contributor.author | Malezieux, Meryl | - |
dc.contributor.author | Gonçalves, Francisco Q. | - |
dc.contributor.author | Grosjean, Noëlle | - |
dc.contributor.author | Blanchet, Christophe | - |
dc.contributor.author | Frick, Andreas | - |
dc.contributor.author | Nägerl, U Valentin | - |
dc.contributor.author | Cunha, Rodrigo A. | - |
dc.contributor.author | Mulle, Christophe | - |
dc.date.accessioned | 2023-09-08T11:38:12Z | - |
dc.date.available | 2023-09-08T11:38:12Z | - |
dc.date.issued | 2016-06-17 | - |
dc.identifier.issn | 2041-1723 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/108713 | - |
dc.description.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. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | 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 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Adenosine A2 Receptor Antagonists | pt |
dc.subject.mesh | Alzheimer Disease | pt |
dc.subject.mesh | Amyloid beta-Protein Precursor | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | CA3 Region, Hippocampal | pt |
dc.subject.mesh | Dendritic Spines | pt |
dc.subject.mesh | Disease Models, Animal | pt |
dc.subject.mesh | Gene Expression Regulation | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Long-Term Potentiation | pt |
dc.subject.mesh | Memory, Episodic | pt |
dc.subject.mesh | Mice | pt |
dc.subject.mesh | Mice, Transgenic | pt |
dc.subject.mesh | Neuroprotective Agents | pt |
dc.subject.mesh | Presenilin-1 | pt |
dc.subject.mesh | Pyrimidines | pt |
dc.subject.mesh | RNA, Small Interfering | pt |
dc.subject.mesh | Receptor, Adenosine A2A | pt |
dc.subject.mesh | Receptors, N-Methyl-D-Aspartate | pt |
dc.subject.mesh | Signal Transduction | pt |
dc.subject.mesh | Synapses | pt |
dc.subject.mesh | Triazines | pt |
dc.subject.mesh | Triazoles | pt |
dc.title | Early synaptic deficits in the APP/PS1 mouse model of Alzheimer's disease involve neuronal adenosine A2A receptors | pt |
dc.type | article | - |
degois.publication.firstPage | 11915 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Nature Communications | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1038/ncomms11915 | pt |
degois.publication.volume | 7 | pt |
dc.date.embargo | 2016-06-17 | * |
uc.date.periodoEmbargo | 0 | pt |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | article | - |
item.languageiso639-1 | en | - |
item.fulltext | Com Texto completo | - |
item.cerifentitytype | Publications | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0003-3182-6289 | - |
crisitem.author.orcid | 0000-0001-8042-0221 | - |
crisitem.author.orcid | 0000-0003-2550-6422 | - |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Early-synaptic-deficits-in-the-APPPS1-mouse-model-of-Alzheimers-disease-involve-neuronal-adenosine-Asub2Asub-receptorsNature-Communications.pdf | 2.16 MB | Adobe PDF | View/Open |
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