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Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury
Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954417/ https://www.ncbi.nlm.nih.gov/pubmed/36831195 http://dx.doi.org/10.3390/cells12040528 |
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author | Bringuier, Claire Mathilde Noristani, Harun Najib Perez, Jean-Christophe Cardoso, Maida Goze-Bac, Christophe Gerber, Yannick Nicolas Perrin, Florence Evelyne |
author_facet | Bringuier, Claire Mathilde Noristani, Harun Najib Perez, Jean-Christophe Cardoso, Maida Goze-Bac, Christophe Gerber, Yannick Nicolas Perrin, Florence Evelyne |
author_sort | Bringuier, Claire Mathilde |
collection | PubMed |
description | Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident astrocytes surrounding the lesion spontaneously transdifferentiate towards a neuronal phenotype. Moreover, this conversion is associated with an increased expression of fibroblast growth factor receptor 4 (Fgfr4), a neural stem cell marker, in astrocytes. Here, we evaluate the therapeutic potential of gene therapy upon Fgfr4 over-expression in mature astrocytes following SCI in adult mice. We found that Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery; however, it may display sexual dimorphism. Improved functional recovery is associated with a decrease in spinal cord lesion volume and reduced glial reactivity. Cell-specific transcriptomic profiling revealed concomitant downregulation of Notch signaling, and up-regulation of neurogenic pathways in converting astrocytes. Our findings suggest that gene therapy targeting Fgfr4 over-expression in astrocytes after injury is a feasible therapeutic approach to improve recovery following traumatism of the spinal cord. Moreover, we stress that a sex-dependent response to astrocytic modulation should be considered for the development of effective translational strategies in other neurological disorders. |
format | Online Article Text |
id | pubmed-9954417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99544172023-02-25 Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury Bringuier, Claire Mathilde Noristani, Harun Najib Perez, Jean-Christophe Cardoso, Maida Goze-Bac, Christophe Gerber, Yannick Nicolas Perrin, Florence Evelyne Cells Article Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident astrocytes surrounding the lesion spontaneously transdifferentiate towards a neuronal phenotype. Moreover, this conversion is associated with an increased expression of fibroblast growth factor receptor 4 (Fgfr4), a neural stem cell marker, in astrocytes. Here, we evaluate the therapeutic potential of gene therapy upon Fgfr4 over-expression in mature astrocytes following SCI in adult mice. We found that Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery; however, it may display sexual dimorphism. Improved functional recovery is associated with a decrease in spinal cord lesion volume and reduced glial reactivity. Cell-specific transcriptomic profiling revealed concomitant downregulation of Notch signaling, and up-regulation of neurogenic pathways in converting astrocytes. Our findings suggest that gene therapy targeting Fgfr4 over-expression in astrocytes after injury is a feasible therapeutic approach to improve recovery following traumatism of the spinal cord. Moreover, we stress that a sex-dependent response to astrocytic modulation should be considered for the development of effective translational strategies in other neurological disorders. MDPI 2023-02-06 /pmc/articles/PMC9954417/ /pubmed/36831195 http://dx.doi.org/10.3390/cells12040528 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bringuier, Claire Mathilde Noristani, Harun Najib Perez, Jean-Christophe Cardoso, Maida Goze-Bac, Christophe Gerber, Yannick Nicolas Perrin, Florence Evelyne Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury |
title | Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury |
title_full | Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury |
title_fullStr | Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury |
title_full_unstemmed | Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury |
title_short | Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury |
title_sort | up-regulation of astrocytic fgfr4 expression in adult mice after spinal cord injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954417/ https://www.ncbi.nlm.nih.gov/pubmed/36831195 http://dx.doi.org/10.3390/cells12040528 |
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