Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/101263
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dc.contributor.authorMoreira-de-Sá, Ana-
dc.contributor.authorGonçalves, Francisco Q.-
dc.contributor.authorLopes, João P.-
dc.contributor.authorSilva, Henrique B.-
dc.contributor.authorTomé, Ângelo R.-
dc.contributor.authorCunha, Rodrigo A.-
dc.contributor.authorCanas, Paula-
dc.date.accessioned2022-08-18T10:55:50Z-
dc.date.available2022-08-18T10:55:50Z-
dc.date.issued2020-
dc.identifier.issn09699961pt
dc.identifier.urihttps://hdl.handle.net/10316/101263-
dc.description.abstractAngelman syndrome (AS) is a neurodevelopmental disorder caused by loss of function of the maternally inherited Ube3a neuronal protein, whose main features comprise severe intellectual disabilities and motor impairments. Previous studies with the Ube3am-/p+ mouse model of AS revealed deficits in synaptic plasticity and memory. Since adenosine A2A receptors (A2AR) are powerful modulators of aberrant synaptic plasticity and A2AR blockade prevents memory dysfunction in various brain diseases, we tested if A2AR could control deficits of memory and hippocampal synaptic plasticity in AS. We observed that Ube3am-/p+ mice were unable to resort to hippocampal-dependent search strategies when tested for learning and memory in the Morris water maze; this was associated with a decreased magnitude of long-term depression (LTD) in CA1 hippocampal circuits. There was an increased density of A2AR in the hippocampus of Ube3am-/p+ mice and their chronic treatment with the selective A2AR antagonist SCH58261 (0.1 mg/kg/day, ip) restored both hippocampal-dependent learning strategies, as well as LTD deficits. Altogether, this study provides the first evidence of a role of A2AR as a new prospective therapeutic target to manage learning deficits in AS.pt
dc.description.sponsorshipThis research work was supported by Fundação Amélia de Mellopt
dc.language.isoengpt
dc.relationFundação Amélia de Mellopt
dc.relationCENTRO-01-0145-FEDER-000008:BrainHealth 2020pt
dc.relationCENTRO-01-0246-FEDER-000010pt
dc.relationPOCI-01-0145-FEDER-031274pt
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04539/2020/PTpt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt
dc.subjectAdenosine A(2A) receptorpt
dc.subjectAngelman syndromept
dc.subjectHippocampuspt
dc.subjectMouse modelpt
dc.subjectSynaptic plasticitypt
dc.subjectUbe3apt
dc.subject.meshAdenosinept
dc.subject.meshAngelman Syndromept
dc.subject.meshAnimalspt
dc.subject.meshDisease Models, Animalpt
dc.subject.meshHippocampuspt
dc.subject.meshLearningpt
dc.subject.meshMemorypt
dc.subject.meshMicept
dc.subject.meshMice, Inbred C57BLpt
dc.subject.meshNeuronal Plasticitypt
dc.titleAdenosine A2A receptors format long-term depression and memory strategies in a mouse model of Angelman syndromept
dc.typearticle-
degois.publication.firstPage105137pt
degois.publication.titleNeurobiology of Diseasept
dc.peerreviewedyespt
dc.identifier.doi10.1016/j.nbd.2020.105137pt
degois.publication.volume146pt
dc.date.embargo2020-01-01*
uc.date.periodoEmbargo0pt
item.grantfulltextopen-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.openairetypearticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextCom Texto completo-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-5468-2647-
crisitem.author.orcid0000-0001-8042-0221-
crisitem.author.orcid0000-0002-5122-1802-
crisitem.author.orcid0000-0002-7234-3411-
crisitem.author.orcid0000-0001-8671-989X-
crisitem.author.orcid0000-0003-2550-6422-
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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