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Título: | Adenosine A2A Receptor Up-Regulation Pre-Dates Deficits of Synaptic Plasticity and of Memory in Mice Exposed to Aβ1-42 to Model Early Alzheimer's Disease | Autor: | Lopes, Cátia R. Silva, Antonio C. Silva, Henrique B. Canas, Paula M. Agostinho, Paula M. Cunha, Rodrigo A. Lopes, João Pedro |
Palavras-chave: | adenosine; A2A receptor; Alzheimer’s disease; memory; LTP; synapse | Data: | 28-Jul-2023 | Editora: | MDPI | Projeto: | Supported by La Caixa Foundation (LCF/PR/HP17/52190001), Centro 2020 (CENTRO- 01-0145-FEDER-000008:BrainHealth2020 and CENTRO-01-0246-FEDER-000010) and FCT (POCI-01- 0145-FEDER-03127 and UIDB/04539/2020). Cátia R. Lopes is under receipt of a PhD grant from FCT (2021.06954.BD) | Título da revista, periódico, livro ou evento: | Biomolecules | Volume: | 13 | Número: | 8 | Resumo: | The intracerebroventricular (icv) injection of amyloid peptides (Aβ) models Alzheimer's disease (AD) in mice, as typified by the onset within 15 days of deficits of memory and of hippocampal long-term potentiation (LTP) that are prevented by the blockade of adenosine A2A receptors (A2AR). Since A2AR overfunction is sufficient to trigger memory deficits, we tested if A2AR were upregulated in hippocampal synapses before the onset of memory deficits to support the hypothesis that A2AR overfunction could be a trigger of AD. Six to eight days after Aβ-icv injection, mice displayed no alterations of hippocampal dependent memory; however, they presented an increased excitability of hippocampal synapses, a slight increase in LTP magnitude in Schaffer fiber-CA1 pyramid synapses and an increased density of A2AR in hippocampal synapses. A2AR blockade with SCH58261 (50 nM) normalized excitability and LTP in hippocampal slices from mice sacrificed 7-8 days after Aβ-icv injection. Fifteen days after Aβ-icv injection, mice displayed evident deficits of hippocampal-dependent memory deterioration, with reduced hippocampal CA1 LTP but no hyperexcitability and a sustained increase in synaptic A2AR, which blockade restored LTP magnitude. This shows that the upregulation of synaptic A2AR precedes the onset of deterioration of memory and of hippocampal synaptic plasticity, supporting the hypothesis that the overfunction of synaptic A2AR could be a trigger of memory deterioration in AD. | URI: | https://hdl.handle.net/10316/112186 | ISSN: | 2218-273X | DOI: | 10.3390/biom13081173 | Direitos: | openAccess |
Aparece nas coleções: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Adenosine-Asub2Asub-Receptor-UpRegulation-PreDates-Deficits-of-Synaptic-Plasticity-and-of-Memory-in-Mice-Exposed-to-Asub142sub-to-Model-Early-Alzheimers-DiseaseBiomolecules.pdf | 1.84 MB | Adobe PDF | Ver/Abrir |
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