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A2A adenosine receptor deletion is protective in a mouse model of Tauopathy

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dc.contributor.authorLaurent, C.
dc.contributor.authorBurnouf, S.
dc.contributor.authorFerry, B.
dc.contributor.authorBatalha, Vânia
dc.contributor.authorCoelho, Joana E
dc.contributor.authorBaqi, Y.
dc.contributor.authorMalik, E.
dc.contributor.authorMariciniak, E.
dc.contributor.authorParrot, S.
dc.contributor.authorVan der Jeugd, A.
dc.contributor.authorFaivre, E.
dc.contributor.authorFlaten, V.
dc.contributor.authorLedent, C.
dc.contributor.authorD'Hooge, R.
dc.contributor.authorSergeant, N.
dc.contributor.authorHamdane, M.
dc.contributor.authorHumez, S.
dc.contributor.authorMüller, C. E.
dc.contributor.authorLopes, Luisa V.
dc.contributor.authorBuée, L.
dc.contributor.authorBlum, D.
dc.date.accessioned2022-06-21T14:58:17Z
dc.date.available2022-06-21T14:58:17Z
dc.date.issued2014
dc.description© 2016 Macmillan Publishers Limited All rights reserved. This work is licensed under a Creative Commons Attribution- NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.description.abstractConsumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.pt_PT
dc.description.sponsorshipThis work was supported by grants from France Alzheimer (to DB) and LECMA/Alzheimer Forschung Initiative (to DB and CEM). DB and LVL got a Égide/Pessoa program EU exchange grant. Our laboratory is also supported by the LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease), Inserm, CNRS, Université Lille 2, Lille Métropole Communauté Urbaine, Région Nord/Pas-de-Calais, FEDER, DN2M, ANR (ADONTAGE and ADORATAU, to DB) and FUI MEDIALZ. We thank the animal facility of IMPRT-IFR114 and M Besegher, I Brion, D Cappe, R Dehaynin, J Devassine, Y Lepage, C Meunier and D Taillieu for transgenic mouse production and animal care, as well as M Basquin, D Demeyer, S Eddarkaoui, H Obriot and M Schneider for support. CL holds a doctoral grant from Lille 2 University, and SB from Région Nord Pas de Calais and CHRU de Lille. VF holds a grant from Région Nord-Pas-de-Calais and Inserm. EF holds a post-doctoral grant from Région Nord-Pas-de-Calais (DN2M). LVL is an Investigator FCT (Fundação para a Ciência e Tecnologia, Portugal).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMol Psychiatry . 2016 Jan;21(1):97-107pt_PT
dc.identifier.doi10.1038/mp.2014.151pt_PT
dc.identifier.eissn1476-5578
dc.identifier.issn1359-4184
dc.identifier.urihttp://hdl.handle.net/10451/53424
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.nature.com/mp/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.titleA2A adenosine receptor deletion is protective in a mouse model of Tauopathypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage107pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage97pt_PT
oaire.citation.titleMolecular Psychiatrypt_PT
oaire.citation.volume21pt_PT
person.familyNameBatalha
person.familyNameCoelho
person.familyNameLopes
person.givenNameVânia
person.givenNameJoana
person.givenNameLuisa
person.identifier149432
person.identifier.ciencia-idA915-3406-B4D3
person.identifier.ciencia-idB310-839B-564D
person.identifier.ciencia-id4817-7194-C024
person.identifier.orcid0000-0001-6657-1111
person.identifier.orcid0000-0002-3964-6197
person.identifier.orcid0000-0001-8367-3005
person.identifier.scopus-author-id7101840699
person.identifier.scopus-author-id7102509159
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationb5815f9d-8015-49d7-ba21-f1e3d899b78d
relation.isAuthorOfPublication1301afd3-8056-4d54-983c-0bec935b2d75
relation.isAuthorOfPublicationdfc15976-b186-45d1-be1c-4592b336edb1
relation.isAuthorOfPublication.latestForDiscoverydfc15976-b186-45d1-be1c-4592b336edb1

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