Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1

Lesioned axons do not regenerate in the adult mammalian central nervous system, owing to the overexpression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have...

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Autores: Seira Oriach, Oscar, Gavín Marín, Rosalina, Gil Fernández, Vanessa, Llorens Torres, Franc, Rangel Rincones, Alejandra Helena, Soriano García, Eduardo, Río Fernández, José Antonio del
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2010
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/36363
Acceso en línea:https://hdl.handle.net/2445/36363
Access Level:acceso abierto
Palabra clave:Neurones
Neurobiologia
Regeneració del sistema nerviós
Neurons
Neurobiology
Nervous system regeneration
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spelling Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1Seira Oriach, OscarGavín Marín, RosalinaGil Fernández, VanessaLlorens Torres, FrancRangel Rincones, Alejandra HelenaSoriano García, EduardoRío Fernández, José Antonio delNeuronesNeurobiologiaRegeneració del sistema nerviósNeuronsNeurobiologyNervous system regenerationLesioned axons do not regenerate in the adult mammalian central nervous system, owing to the overexpression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For myelin-associated inhibition, blockage with NEP1-40, receptor bodies or IN-1 antibodies has been used. In addition, endogenous blockage of cell signalling mechanisms induced by myelin-associated proteins is a potential tool for overcoming axon inhibitory signals. We examined the participation of glycogen synthase kinase 3 (GSK3) and ERK1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3 and ERK1/2 activities facilitates regeneration after myelin-directed inhibition in two models: i) cerebellar granule cells and ii) lesioned entorhino-hippocampal pathway in slice cultures, and whether the regenerative effects are mediated by Nogo Receptor 1 (NgR1). We demonstrate that, in contrast to ERK1/2 inhibition, the pharmacological treatment of GSK3 inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Lastly these regenerative effects were corroborated in the lesioned EHP in NgR1 -/- mutant mice. These results provide new findings for the development of new assays and strategies to enhance axon regeneration in injured cortical connections.Wiley2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionapplication/pdfhttps://hdl.handle.net/2445/36363Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió preprint del document publicat a: http://dx.doi.org/10.1111/j.1471-4159.2010.06726.xJournal of Neurochemistry, 2010, vol. 113, num. 6, p. 1644-1658http://dx.doi.org/10.1111/j.1471-4159.2010.06726.x(c) International Society for Neurochemistry, 2010info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/363632026-05-27T06:46:51Z
dc.title.none.fl_str_mv Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
title Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
spellingShingle Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
Seira Oriach, Oscar
Neurones
Neurobiologia
Regeneració del sistema nerviós
Neurons
Neurobiology
Nervous system regeneration
title_short Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
title_full Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
title_fullStr Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
title_full_unstemmed Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
title_sort Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
dc.creator.none.fl_str_mv Seira Oriach, Oscar
Gavín Marín, Rosalina
Gil Fernández, Vanessa
Llorens Torres, Franc
Rangel Rincones, Alejandra Helena
Soriano García, Eduardo
Río Fernández, José Antonio del
author Seira Oriach, Oscar
author_facet Seira Oriach, Oscar
Gavín Marín, Rosalina
Gil Fernández, Vanessa
Llorens Torres, Franc
Rangel Rincones, Alejandra Helena
Soriano García, Eduardo
Río Fernández, José Antonio del
author_role author
author2 Gavín Marín, Rosalina
Gil Fernández, Vanessa
Llorens Torres, Franc
Rangel Rincones, Alejandra Helena
Soriano García, Eduardo
Río Fernández, José Antonio del
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Neurones
Neurobiologia
Regeneració del sistema nerviós
Neurons
Neurobiology
Nervous system regeneration
topic Neurones
Neurobiologia
Regeneració del sistema nerviós
Neurons
Neurobiology
Nervous system regeneration
description Lesioned axons do not regenerate in the adult mammalian central nervous system, owing to the overexpression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For myelin-associated inhibition, blockage with NEP1-40, receptor bodies or IN-1 antibodies has been used. In addition, endogenous blockage of cell signalling mechanisms induced by myelin-associated proteins is a potential tool for overcoming axon inhibitory signals. We examined the participation of glycogen synthase kinase 3 (GSK3) and ERK1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3 and ERK1/2 activities facilitates regeneration after myelin-directed inhibition in two models: i) cerebellar granule cells and ii) lesioned entorhino-hippocampal pathway in slice cultures, and whether the regenerative effects are mediated by Nogo Receptor 1 (NgR1). We demonstrate that, in contrast to ERK1/2 inhibition, the pharmacological treatment of GSK3 inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Lastly these regenerative effects were corroborated in the lesioned EHP in NgR1 -/- mutant mice. These results provide new findings for the development of new assays and strategies to enhance axon regeneration in injured cortical connections.
publishDate 2010
dc.date.none.fl_str_mv 2010
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/submittedVersion
format article
status_str submittedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/36363
url https://hdl.handle.net/2445/36363
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió preprint del document publicat a: http://dx.doi.org/10.1111/j.1471-4159.2010.06726.x
Journal of Neurochemistry, 2010, vol. 113, num. 6, p. 1644-1658
http://dx.doi.org/10.1111/j.1471-4159.2010.06726.x
dc.rights.none.fl_str_mv (c) International Society for Neurochemistry, 2010
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) International Society for Neurochemistry, 2010
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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