Nurr1 protein Is required for N-methyl-d-aspartic acid (NMDA) receptor-mediated neuronal survival
Author
Barneda-Zahonero, Bruna
Servitja, Joan-Marc
Badiola, Nahuai
Miñano Molina, Alfredo Jesús
Fadó Andrés, Rut
Saura, Carlos A.
Rodríguez-Álvarez, José
Publication date
2012-03-30ISSN
0021-9258
Abstract
NMDA 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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Neurones
Cervell -- Evolució
Genomes
Apoptosi
Neuronas
Cerebro -- Evolución
Genomas
Apoptosis
Neurons
Brain -- Evolution
Genomes
Apoptosis
Pages
12
Publisher
Elsevier
Collection
287; 14
Is part of
Journal of Biological Chemistry
Citation
Barneda-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.M111.272427
This item appears in the following Collection(s)
- Ciències de la Salut [745]
Rights
This is an open access article under the CC BY license.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/