dc.contributor.author | Parada, Esther | |
dc.contributor.author | Egea, Javier | |
dc.contributor.author | Buendía, Izaskun | |
dc.contributor.author | Negredo Madrigal, Pilar | |
dc.contributor.author | Cunha, Ana C. | |
dc.contributor.author | Cardoso, Silvia | |
dc.contributor.author | Soares, Miguel P. | |
dc.contributor.author | López, Manuela G. | |
dc.contributor.other | UAM. Departamento de Anatomía, Histología y Neurociencia | es_ES |
dc.contributor.other | UAM. Departamento de Farmacología | es_ES |
dc.date.accessioned | 2014-12-18T11:47:04Z | |
dc.date.available | 2014-12-18T11:47:04Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Antioxidants & Redox Signaling 19.11 ( 2013): 1135-1148 | en_US |
dc.identifier.issn | 1523-0864 (print) | en_US |
dc.identifier.issn | 1557-7716 (online) | en_US |
dc.identifier.uri | http://hdl.handle.net/10486/662894 | |
dc.description | This is copy of an article published in the Antioxidants & Redox Signaling © 2013 Mary Ann Liebert, Inc. Antioxidants& Redox Signalingi available online at: http://online.liebertpub.com | en_US |
dc.description.abstract | We asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic
event acts via a mechanism involving the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or
the expression of its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, the protective effect of the
pharmacologic alpha-7 nicotinic acetylcholine receptor (a7 nAChR) agonist PNU282987 was analyzed in organotypic
hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) in vitro as well as in
photothrombotic stroke in vivo. Results: OHCs exposed to OGD followed by reoxygenation elicited cell death,
measured by propidium iodide and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining. Activation
of a7 nAChR by PNU282987, after OGD, reduced cell death, reactive oxygen species production, and
tumor necrosis factor release. This was associated with induction of HO-1 expression, an effect reversed by abungarotoxin
and by tin–protoporphyrin IX. The protective effect of PNU282987 was lost in microglial-depleted
OHCs as well as in OHCs from Nrf2-deficient-versus-wild-type mice, an effect associated with suppression of HO-
1 expression in microglia. Administration of PNU282987 1 h after induction of photothrombotic stroke in vivo
reduced the infarct size and improved motor skills in Hmox1lox/lox mice that express normal levels of HO-1, but not
in LysMCreHmox1D/D in which HO-1 expression is inhibited in myeloid cells, including the microglia. Innovation:
This study suggests the participation of the microglial a7 nAChR in the brain cholinergic anti-inflammatory
pathway. Conclusion: Activation of the a7 nAChR/Nrf2/HO-1 axis in microglia regulates neuroinflammation and
oxidative stress, affording neuroprotection under brain ischemic conditions. Antioxid. Redox Signal. 19, 1135–1148 | en_US |
dc.description.sponsorship | This work was supported in part by grants from Spanish
Ministry of Science and Innovation Ref. SAF2009-12150 and
SAF2012-32223 and the Spanish Ministry of Health (Instituto
de Salud Carlos III) RETICS-RD06/0026 to MGL. E.P. and I.B.
have a predoctoral fellowship from the Spanish Ministry of
Economy. We would also like to thank the Fundacion Teofilo
Hernando for its continued support. Funding: Fundac¸ao para
a Ciencia e Tecnologia (Portugal) grants to MPS: PTDC/BIABCM/
101311/2008, PTDC/SAU-FCF/100762/2008, and
PTDC/SAU-TOX/116627/2010) and European Community
6th Framework Grant LSH-2005-1.2.5-1 and 7th Framework
Grant ERC-2011-AdG. 294709–DAMAGECONTROL. Ana
Cunha was supported by a fellowship within the project
PTDC/SAU-FCF/100762/2008 awarded to MPS | en_US |
dc.format.extent | 14 pag. | en |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | es_ES |
dc.publisher | Mary Ann Liebert, Inc. | en_US |
dc.relation.ispartof | Antioxidants & Redox Signaling | en_US |
dc.rights | © Mary Ann Liebert, Inc. | en_US |
dc.subject.other | Receptor nicotinic | en_US |
dc.subject.other | Neuroprotection | en_US |
dc.subject.other | Factor Erythroid | en_US |
dc.title | The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2 | en_US |
dc.type | article | en |
dc.subject.eciencia | Medicina | es_ES |
dc.relation.publisherversion | http://dx.doi.org/10.1089/ars.2012.4671 | es_ES |
dc.identifier.doi | 10.1089/ars.2012.4671 | es_ES |
dc.identifier.publicationfirstpage | 1135 | es_ES |
dc.identifier.publicationissue | 11 | es_ES |
dc.identifier.publicationlastpage | 1148 | es_ES |
dc.identifier.publicationvolume | 19 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/294709 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Cardoso Leao , Sylvia (267631) | |
dc.facultadUAM | Facultad de Medicina | |
dc.institutoUAM | Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) | |
dc.institutoUAM | Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa) | |