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Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats

Spinal cord injury (SCI) is a severe condition that affects many people and results in high health care costs. Therefore, it is essential to find new targets for treatment. The fibroblast growth factor receptor 1 (FGFR1) signalling pathway has a history of being explored for SCI treatment. Several g...

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Autores principales: Haenzi, Barbara, Gers-Barlag, Katharina, Akhoundzadeh, Halima, Hutson, Thomas H., Menezes, Sean C., Bunge, Mary Bartlett, Moon, Lawrence D. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807820/
https://www.ncbi.nlm.nih.gov/pubmed/27015635
http://dx.doi.org/10.1371/journal.pone.0150541
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author Haenzi, Barbara
Gers-Barlag, Katharina
Akhoundzadeh, Halima
Hutson, Thomas H.
Menezes, Sean C.
Bunge, Mary Bartlett
Moon, Lawrence D. F.
author_facet Haenzi, Barbara
Gers-Barlag, Katharina
Akhoundzadeh, Halima
Hutson, Thomas H.
Menezes, Sean C.
Bunge, Mary Bartlett
Moon, Lawrence D. F.
author_sort Haenzi, Barbara
collection PubMed
description Spinal cord injury (SCI) is a severe condition that affects many people and results in high health care costs. Therefore, it is essential to find new targets for treatment. The fibroblast growth factor receptor 1 (FGFR1) signalling pathway has a history of being explored for SCI treatment. Several groups have examined the effect of high availability of different FGFR1 ligands at the injury site and reported corticospinal tract (CST) regeneration as well as improved motor functions. In this study, we investigated overexpression of the FGFR1 in rat corticospinal neurons in vivo after injury (unilateral pyramidotomy) and in cerebellar granule neurons (CGNs) in vitro. We show that overexpression of FGFR1 using AAV1 intracortical injections did not increase sprouting of the treated corticospinal tract and did not improve dexterity or walking in a rat model of SCI. Furthermore, we show that overexpression of FGFR1 in vitro resulted in decreased neurite outgrowth compared to control. Thus, our results suggest that the FGFR1 is not a suitable therapeutic target after SCI.
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spelling pubmed-48078202016-04-05 Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats Haenzi, Barbara Gers-Barlag, Katharina Akhoundzadeh, Halima Hutson, Thomas H. Menezes, Sean C. Bunge, Mary Bartlett Moon, Lawrence D. F. PLoS One Research Article Spinal cord injury (SCI) is a severe condition that affects many people and results in high health care costs. Therefore, it is essential to find new targets for treatment. The fibroblast growth factor receptor 1 (FGFR1) signalling pathway has a history of being explored for SCI treatment. Several groups have examined the effect of high availability of different FGFR1 ligands at the injury site and reported corticospinal tract (CST) regeneration as well as improved motor functions. In this study, we investigated overexpression of the FGFR1 in rat corticospinal neurons in vivo after injury (unilateral pyramidotomy) and in cerebellar granule neurons (CGNs) in vitro. We show that overexpression of FGFR1 using AAV1 intracortical injections did not increase sprouting of the treated corticospinal tract and did not improve dexterity or walking in a rat model of SCI. Furthermore, we show that overexpression of FGFR1 in vitro resulted in decreased neurite outgrowth compared to control. Thus, our results suggest that the FGFR1 is not a suitable therapeutic target after SCI. Public Library of Science 2016-03-25 /pmc/articles/PMC4807820/ /pubmed/27015635 http://dx.doi.org/10.1371/journal.pone.0150541 Text en © 2016 Haenzi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Haenzi, Barbara
Gers-Barlag, Katharina
Akhoundzadeh, Halima
Hutson, Thomas H.
Menezes, Sean C.
Bunge, Mary Bartlett
Moon, Lawrence D. F.
Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats
title Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats
title_full Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats
title_fullStr Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats
title_full_unstemmed Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats
title_short Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats
title_sort overexpression of the fibroblast growth factor receptor 1 (fgfr1) in a model of spinal cord injury in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807820/
https://www.ncbi.nlm.nih.gov/pubmed/27015635
http://dx.doi.org/10.1371/journal.pone.0150541
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