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dc.contributor.author
Dupraz, Sebastian, Enrique
dc.contributor.author
Grassi, Diego Javier
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dc.contributor.author
Karnas, Diana
dc.contributor.author
Nieto Guil, Alvaro Fernando
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dc.contributor.author
Hicks, David
dc.contributor.author
Quiroga, Santiago
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dc.date.available
2015-06-03T18:35:25Z
dc.date.issued
2013-01
dc.identifier.citation
Dupraz, Sebastian Enrique; Grassi, Diego Javier; Karnas, Diana; Nieto Guil, Alvaro Fernando; Hicks, David; Quiroga, Santiago; The Insulin-Like Growth Factor 1 Receptor Is Essential for Axonal Regeneration in Adult Central Nervous System Neurons. PLoS ONE 1-2013 8(1): e54462. doi:10.1371/journal.pone.0054462
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/591
dc.description.abstract
Axonal regeneration is an essential condition to re-establish functional neuronal connections in the injured adult central nervous system (CNS), but efficient regrowth of severed axons has proven to be very difficult to achieve. Although significant progress has been made in identifying the intrinsic and extrinsic mechanisms involved, many aspects remain unresolved. Axonal development in embryonic CNS (hippocampus) requires the obligate activation of the insulin-like growth factor 1 receptor (IGF-1R). Based on known similarities between axonal growth in fetal compared to mature CNS, we decided to examine the expression of the IGF-1R, using an antibody to the βgc subunit or a polyclonal anti-peptide antibody directed to the IGF-R (C20), in an in vitro model of adult CNS axonal regeneration, namely retinal ganglion cells (RGC) derived from adult rat retinas. Expression of both βgc and the β subunit recognized by C20 antibody were low in freshly isolated adult RGC, but increased significantly after 4 days in vitro. As in embryonic axons, βgc was localised to distal regions and leading growth cones in RGC. IGF-1R-βgc co-localised with activated p85 involved in the phosphatidylinositol-3 kinase (PI3K) signaling pathway, upon stimulation with IGF-1. Blocking experiments using either an antibody which neutralises IGF-1R activation, shRNA designed against the IGF-1R sequence, or the PI3K pathway inhibitor LY294002, all significantly reduced axon regeneration from adult RGC in vitro (∼40% RGC possessed axons in controls vs 2-8% in the different blocking studies). Finally, co-transfection of RGC with shRNA to silence IGF-1R together with a vector containing a constitutively active form of downstream PI3K (p110), fully restored axonal outgrowth in vitro. Hence these data demonstrate that axonal regeneration in adult CNS neurons requires re-expression and activation of IGF-1R, and targeting this system may offer new therapeutic approaches to enhancing axonal regeneration following trauma.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library Science
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Axonal Regeneration
dc.subject
Retinal Ganglion Cells
dc.subject
Igf-1 Receptor
dc.subject
Adult Cns
dc.subject.classification
Ciencias Naturales y Exactas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
Bioquímica y Biología Molecular (ídem 3.1.10)
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dc.title
The insulin-like growth factor 1 receptor is essential for axonal regeneration in adult central nervous system neurons
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
8
dc.journal.number
1
dc.journal.pagination
e-54462
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Dupraz, Sebastian, Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.description.fil
Fil: Grassi, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.description.fil
Fil: Karnas, Diana. Rhythms, Life and Death in the Retina. Centre National de la Recherche Scientifique (CNRS). Université de Strasbourg. Institut des Neurosciences Cellulaires et Intégratives; France;
dc.description.fil
Fil: Nieto Guil, Alvaro Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.description.fil
Fil: Hicks, David. Rhythms, Life and Death in the Retina. Centre National de la Recherche Scientifique (CNRS). Université de Strasbourg. Institut des Neurosciences Cellulaires et Intégratives; France;
dc.description.fil
Fil: Quiroga, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.journal.title
Plos One
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0054462
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