| Metadato | Etiqueta | Valor | Idioma |
|---|---|---|---|
| dc.contributor.author | Autor | Kovacs, Mariángeles | - |
| dc.contributor.author | Autor | Alamón, Catalina | - |
| dc.contributor.author | Autor | Maciel, Cecilia | - |
| dc.contributor.author | Autor | Varela, Valentina | - |
| dc.contributor.author | Autor | Ibarburu, Sofía | - |
| dc.contributor.author | Autor | Tarrago, Lucas | - |
| dc.contributor.author | Autor | King, Peter H. | - |
| dc.contributor.author | Autor | Si, Ying | - |
| dc.contributor.author | Autor | Kwon, Yuri | - |
| dc.contributor.author | Autor | Hermine, Olivier | - |
| dc.contributor.author | Autor | Barbeito, Luis | - |
| dc.contributor.author | Autor | Trias, Emiliano | - |
| dc.contributor.filiacion | Filiación | Kovacs Mariángeles, Instituto Pasteur (Montevideo). | - |
| dc.contributor.filiacion | Filiación | Alamón Catalina, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica. | - |
| dc.contributor.filiacion | Filiación | Maciel Cecilia, Instituto Pasteur (Montevideo). | - |
| dc.contributor.filiacion | Filiación | Varela Valentina, Instituto Pasteur (Montevideo). | - |
| dc.contributor.filiacion | Filiación | Ibarburu Sofía, Instituto Pasteur (Montevideo). | - |
| dc.contributor.filiacion | Filiación | Tarrago Lucas, Instituto Pasteur (Montevideo). | - |
| dc.contributor.filiacion | Filiación | King Peter H. | - |
| dc.contributor.filiacion | Filiación | Si Ying | - |
| dc.contributor.filiacion | Filiación | Kwon Yuri | - |
| dc.contributor.filiacion | Filiación | Hermine Olivier | - |
| dc.contributor.filiacion | Filiación | Barbeito Luis, Instituto Pasteur (Montevideo). | - |
| dc.contributor.filiacion | Filiación | Trias Emiliano, Instituto Pasteur (Montevideo). | - |
| dc.date.accessioned | Fecha ingreso | 2023-06-02T17:44:47Z | - |
| dc.date.available | Fecha disponible | 2023-06-02T17:44:47Z | - |
| dc.date.issued | Año de publicación | 2021 | - |
| dc.description.abstract | Resumen | Degeneration of motor neurons, glial cell reactivity, and vascular alterations in the CNS are important neuropathological features of amyotrophic lateral sclerosis (ALS). Immune cells trafficking from the blood also infiltrate the affected CNS parenchyma and contribute to neuroinflammation. Mast cells (MCs) are hematopoietic-derived immune cells whose precursors differentiate upon migration into tissues. Upon activation, MCs undergo degranulation with the ability to increase vascular permeability, orchestrate neuroinflammation and modulate the neuroimmune response. However, the prevalence, pathological significance, and pharmacology of MCs in the CNS of ALS patients remain largely unknown. In autopsy ALS spinal cords, we identified for the first time that MCs express c-Kit together with chymase, tryptase, and Cox-2 and display granular or degranulating morphology, as compared with scarce MCs in control cords. In ALS, MCs were mainly found in the niche between spinal motor neuron somas and nearby microvascular elements, and they displayed remarkable pathological abnormalities. Similarly, MCs accumulated in the motor neuron-vascular niche of ALS murine models, in the vicinity of astrocytes and motor neurons expressing the c-Kit ligand stem cell factor (SCF), suggesting an SCF/c-Kit-dependent mechanism of MC differentiation from precursors. Mechanistically, we provide evidence that fully differentiated MCs in cell cultures can be generated from the murine ALS spinal cord tissue, further supporting the presence of c-Kit+ MC precursors. Moreover, intravenous administration of bone marrow-derived c-Kit+ MC precursors infiltrated the spinal cord in ALS mice but not in controls, consistent with aberrant trafficking through a defective microvasculature. Pharmacological inhibition of c-Kit with masitinib in ALS mice reduced the MC number and the influx of MC precursors from the periphery. Our results suggest a previously unknown pathogenic mechanism triggered by MCs in the ALS motor neuron-vascular niche that might be targeted pharmacologically. | es |
| dc.format.extent | Extensión | 18 h. | es |
| dc.format.mimetype | Formato | application/pdf | es |
| dc.identifier.citation | Citación | Kovacs, M, Alamón Lima, C, Maciel, C [y otros autores]. "The pathogenic role of c‑Kit+ mast cells in the spinal motor neuron‑vascular niche in ALS". Acta Neuropathologica Communications. [en línea] 2021, 9: 136. 18 h. DOI:10.1186/s40478-021-01241-3. | es |
| dc.identifier.doi | DOI | 10.1186/s40478-021-01241-3 | - |
| dc.identifier.issn | ISSN | 2051-5960 | - |
| dc.identifier.uri | URI | https://hdl.handle.net/20.500.12008/37418 | - |
| dc.language.iso | Idioma | en | es |
| dc.publisher | Editorial | Springer Nature | es |
| dc.relation.ispartof | EN | Acta Neuropathologica Communications, 2021, 9: 136. | es |
| dc.rights | Derechos | Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014) | es |
| dc.rights.licence | Licencia | Licencia Creative Commons Atribución (CC - By 4.0) | es |
| dc.subject | Palabras clave | Mast cells | es |
| dc.subject | Palabras clave | Motor neuron-vascular niche | es |
| dc.subject | Palabras clave | ALS | es |
| dc.subject | Palabras clave | Masitinib | es |
| dc.subject | Palabras clave | Spinal cord | es |
| dc.title | Título | The pathogenic role of c‑Kit+ mast cells in the spinal motor neuron‑vascular niche in ALS | es |
| dc.type | Tipo de documento | Artículo | es |
Colecciones:
| Ficheros | Descripción | Tamaño | Formato | ||
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| Principal 101186s40478021012413.pdf | — | 3.03 MB | Adobe PDF |