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dc.contributor.authorBarneda-Zahonero, Bruna
dc.contributor.authorServitja, Joan-Marc
dc.contributor.authorBadiola, Nahuai
dc.contributor.authorMiñano Molina, Alfredo Jesús
dc.contributor.authorFadó Andrés, Rut
dc.contributor.authorSaura, Carlos A.
dc.contributor.authorRodríguez-Álvarez, José
dc.date.accessioned2021-04-28T16:54:08Z
dc.date.available2021-04-28T16:54:08Z
dc.date.issued2012-03-30
dc.identifier.citationBarneda-Zahonero, Bruna; Servitja, Joan-Marc; Badiola, Nahuai [et al.]. Nurr1 protein Is required for N-methyl-d-aspartic acid (NMDA) receptor-mediated neuronal survival. Journal of Biological Chemistry, 2012, 287(14), p. 11351-11362. Disponible en: <https://www.sciencedirect.com/science/article/pii/S0021925820480718?via%3Dihub>. Fecha de acceso: 28 abr. 2021. DOI: 10.1074/jbc.M111.272427ca
dc.identifier.issn0021-9258ca
dc.identifier.urihttp://hdl.handle.net/20.500.12328/2510
dc.description.abstractNMDA receptor (NMDAR) stimulation promotes neuronal survival during brain development. Cerebellar granule cells (CGCs) need NMDAR stimulation to survive and develop. These neurons differentiate and mature during its migration from the external granular layer to the internal granular layer, and lack of excitatory inputs triggers their apoptotic death. It is possible to mimic this process in vitro by culturing CGCs in low KCl concentrations (5 mm) in the presence or absence of NMDA. Using this experimental approach, we have obtained whole genome expression profiles after 3 and 8 h of NMDA addition to identify genes involved in NMDA-mediated survival of CGCs. One of the identified genes was Nurr1, a member of the orphan nuclear receptor subfamily Nr4a. Our results report a direct regulation of Nurr1 by CREB after NMDAR stimulation. ChIP assay confirmed CREB binding to Nurr1 promoter, whereas CREB shRNA blocked NMDA-mediated increase in Nurr1 expression. Moreover, we show that Nurr1 is important for NMDAR survival effect. We show that Nurr1 binds to Bdnf promoter IV and that silencing Nurr1 by shRNA leads to a decrease in brain-derived neurotrophic factor (BDNF) protein levels and a reduction of NMDA neuroprotective effect. Also, we report that Nurr1 and BDNF show a similar expression pattern during postnatal cerebellar development. Thus, we conclude that Nurr1 is a downstream target of CREB and that it is responsible for the NMDA-mediated increase in BDNF, which is necessary for the NMDA-mediated prosurvival effect on neurons.en
dc.format.extent12ca
dc.language.isoengca
dc.publisherElsevierca
dc.relation.ispartofJournal of Biological Chemistryca
dc.relation.ispartofseries287;14
dc.rightsThis is an open access article under the CC BY license.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.otherNeuronesca
dc.subject.otherCervell -- Evolucióca
dc.subject.otherGenomesca
dc.subject.otherApoptosica
dc.subject.otherNeuronases
dc.subject.otherCerebro -- Evoluciónes
dc.subject.otherGenomases
dc.subject.otherApoptosises
dc.subject.otherNeuronsen
dc.subject.otherBrain -- Evolutionen
dc.subject.otherGenomesen
dc.subject.otherApoptosisen
dc.titleNurr1 protein Is required for N-methyl-d-aspartic acid (NMDA) receptor-mediated neuronal survivalen
dc.typeinfo:eu-repo/semantics/articleca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapca
dc.subject.udc61ca
dc.identifier.doihttps://dx.doi.org/10.1074/jbc.M111.272427ca


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