Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/107549
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Canas, Paula M. | - |
dc.contributor.author | Porciúncula, Lisiane O. | - |
dc.contributor.author | Simões, Ana Patrícia | - |
dc.contributor.author | Augusto, Elisabete de Oliveira | - |
dc.contributor.author | Silva, Henrique B. | - |
dc.contributor.author | Machado, Nuno J. | - |
dc.contributor.author | Gonçalves, Nélio | - |
dc.contributor.author | Alfaro, Tiago M. | - |
dc.contributor.author | Gonçalves, Francisco Q. | - |
dc.contributor.author | Araújo, Inês M. | - |
dc.contributor.author | Real, Joana I. | - |
dc.contributor.author | Coelho, Joana E. | - |
dc.contributor.author | Andrade, Geanne M. | - |
dc.contributor.author | Almeida, Ramiro D. | - |
dc.contributor.author | Chen, Jiang-Fan | - |
dc.contributor.author | Köfalvi, Attila | - |
dc.contributor.author | Agostinho, Paula | - |
dc.contributor.author | Cunha, Rodrigo A. | - |
dc.date.accessioned | 2023-07-19T11:22:54Z | - |
dc.date.available | 2023-07-19T11:22:54Z | - |
dc.date.issued | 2018 | - |
dc.identifier.issn | 2373-2822 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/107549 | - |
dc.description.abstract | Neurodegeneration is a process transversal to neuropsychiatric diseases and the understanding of its mechanisms should allow devising strategies to prevent this irreversible step in brain diseases. Neurodegeneration caused by seizures is a critical step in the aggravation of temporal lobe epilepsy, but its mechanisms remain undetermined. Convulsions trigger an elevation of extracellular adenosine and upregulate adenosine A2A receptors (A2AR), which have been associated with the control of neurodegenerative diseases. Using the rat and mouse kainate model of temporal lobe epilepsy, we now tested whether A2AR control convulsions-induced hippocampal neurodegeneration. The pharmacological or genetic blockade of A2AR did not affect kainate-induced convulsions but dampened the subsequent neurotoxicity. This neurotoxicity began with a rapid A2AR upregulation within glutamatergic synapses (within 2 h), through local translation of synaptic A2AR mRNA. This bolstered A2AR-mediated facilitation of glutamate release and of long-term potentiation (LTP) in CA1 synapses (4 h), triggered a subsequent synaptotoxicity, heralded by decreased synaptic plasticity and loss of synaptic markers coupled to calpain activation (12 h), that predated overt neuronal loss (24 h). All modifications were prevented by the deletion of A2AR selectively in forebrain neurons. This shows that synaptic A2AR critically control synaptic excitotoxicity, which underlies the development of convulsions-induced neurodegeneration. | pt |
dc.language.iso | eng | pt |
dc.publisher | Society for Neuroscience | pt |
dc.relation | Santa Casa da Misericórdia, Faculty of Medicine of the University of Coimbra (FMUC)/Santander-Totta, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para a Ciência e a Tecnologia (FCT), and European Regional Development Fund through Centro 2020 (CENTRO-01-0246-FEDER-000010 and CENTRO-01- 0246-FEDER-000010) and through FCT (POCI-01-0145-FEDER-031274). | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | adenosine | pt |
dc.subject | convulsions | pt |
dc.subject | neuroprotection | pt |
dc.subject | synapse | pt |
dc.subject | synaptotoxicity | pt |
dc.subject | synatic plasticity | pt |
dc.subject.mesh | Adenosine A2 Receptor Antagonists | pt |
dc.subject.mesh | Amygdala | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | Cells, Cultured | pt |
dc.subject.mesh | Convulsants | pt |
dc.subject.mesh | Epilepsy | pt |
dc.subject.mesh | Hippocampus | pt |
dc.subject.mesh | Kainic Acid | pt |
dc.subject.mesh | Kindling, Neurologic | pt |
dc.subject.mesh | Male | pt |
dc.subject.mesh | Mice | pt |
dc.subject.mesh | Mice, Inbred C57BL | pt |
dc.subject.mesh | Mice, Knockout | pt |
dc.subject.mesh | Nerve Degeneration | pt |
dc.subject.mesh | Neurons | pt |
dc.subject.mesh | Protein Binding | pt |
dc.subject.mesh | Pyrimidines | pt |
dc.subject.mesh | Rats | pt |
dc.subject.mesh | Rats, Wistar | pt |
dc.subject.mesh | Receptor, Adenosine A2A | pt |
dc.subject.mesh | Synaptic Transmission | pt |
dc.subject.mesh | Triazoles | pt |
dc.title | Neuronal Adenosine A2A Receptors Are Critical Mediators of Neurodegeneration Triggered by Convulsions | pt |
dc.type | article | - |
degois.publication.firstPage | e0385-18.2018 | pt |
degois.publication.issue | 6 | pt |
degois.publication.title | eNeuro | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1523/ENEURO.0385-18.2018 | pt |
degois.publication.volume | 5 | pt |
dc.date.embargo | 2018-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
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.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-7234-3411 | - |
crisitem.author.orcid | 0000-0001-8042-0221 | - |
crisitem.author.orcid | 0000-0001-9363-4130 | - |
crisitem.author.orcid | 0000-0001-5523-4945 | - |
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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Neuronal-adenosine-A2A-receptors-are-critical-mediators-of-neurodegeneration-triggered-by-convulsionseNeuro.pdf | 3.08 MB | Adobe PDF | View/Open |
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