dc.creator | Gómez Oliva, Ricardo | es |
dc.creator | Geribaldi Doldán, Noelia | es |
dc.creator | Domínguez García, Samuel | es |
dc.creator | Pardillo Díaz, Ricardo | es |
dc.creator | Martínez Ortega, Sergio | es |
dc.creator | Oliva Montero, José M. | es |
dc.creator | Núñez Abades, Pedro Antonio | es |
dc.date.accessioned | 2024-05-15T11:12:29Z | |
dc.date.available | 2024-05-15T11:12:29Z | |
dc.date.issued | 2023-11-30 | |
dc.identifier.citation | Gómez Oliva, R., Geribaldi Doldán, N., Domínguez García, S., Pardillo Díaz, R., Martínez Ortega, S., Oliva Montero, J.M. y Núñez Abades, P.A. (2023). Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries. Journal of Translational Medicine, 21 (1), 867. https://doi.org/10.1186/s12967-023-04707-1. | |
dc.identifier.issn | 1479-5876 | es |
dc.identifier.uri | https://hdl.handle.net/11441/158369 | |
dc.description.abstract | Background Neurogenesis is stimulated in the subventricular zone (SVZ) of mice with cortical brain injuries. In most
of these injuries, newly generated neuroblasts attempt to migrate toward the injury, accumulating within the corpus
callosum not reaching the perilesional area.
Methods We use a murine model of mechanical cortical brain injury, in which we perform unilateral cortical injuries
in the primary motor cortex of adult male mice. We study neurogenesis in the SVZ and perilesional area at 7 and 14
dpi as well as the expression and concentration of the signaling molecule transforming growth factor alpha (TGF-α)
and its receptor the epidermal growth factor (EGFR). We use the EGFR inhibitor Afatinib to promote neurogenesis
in brain injuries.
Results We show that microglial cells that emerge within the injured area and the SVZ in response to the injury
express high levels of TGF-α leading to elevated concentrations of TGF-α in the cerebrospinal fluid. Thus, the number
of neuroblasts in the SVZ increases in response to the injury, a large number of these neuroblasts remain immature
and proliferate expressing the epidermal growth factor receptor (EGFR) and the proliferation marker Ki67. Restraining
TGF-α release with a classical protein kinase C inhibitor reduces the number of these proliferative EGFR+
immature
neuroblasts in the SVZ. In accordance, the inhibition of the TGF-α receptor, EGFR promotes migration of neuroblasts
toward the injury leading to an elevated number of neuroblasts within the perilesional area.
Conclusions Our results indicate that in response to an injury, microglial cells activated within the injury and the SVZ
release TGF-α, activating the EGFR present in the neuroblasts membrane inducing their proliferation, delaying maturation
and negatively regulating migration. The inactivation of this signaling pathway stimulates neuroblast migration
toward the injury and enhances the quantity of neuroblasts within the injured area. These results suggest that these
proteins may be used as target molecules to regenerate brain injuries. | es |
dc.description.sponsorship | Agencia Estatal de Investigación española RTI-2018–099908-B-C21 | es |
dc.description.sponsorship | Consejería de Economía, Conocimiento, Empresas y Universidades. Junta de Andalucía FEDERUCA18-106647 | es |
dc.description.sponsorship | FEDER Andalucía (2014-2020) 2019-0042 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | BMC | es |
dc.relation.ispartof | Journal of Translational Medicine, 21 (1), 867. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Transforming growth factor alpha | es |
dc.subject | Adult neurogenesis | es |
dc.subject | Brain injuries | es |
dc.subject | Neuroblast migration | es |
dc.subject | Neuroregeneration | es |
dc.title | Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología | es |
dc.relation.projectID | RTI-2018–099908-B-C21 | es |
dc.relation.projectID | FEDERUCA18-106647 | es |
dc.relation.projectID | 2019-0042 | es |
dc.relation.publisherversion | https://doi.org/10.1186/s12967-023-04707-1 | es |
dc.identifier.doi | 10.1186/s12967-023-04707-1 | es |
dc.journaltitle | Journal of Translational Medicine | es |
dc.publication.volumen | 21 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 867 | es |
dc.contributor.funder | Agencia Estatal de Investigación. España | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) | es |