Evidence of p75 Neurotrophin Receptor Involvement in the Central Nervous System Pathogenesis of Classical Scrapie in Sheep and a Transgenic Mouse Model
Ver/Abrir
Autor/a
Barrio, Tomás
Betancor, Marina
Otero, Alicia
Martín-Burriel, Inmaculada
Monzón, Marta
Monleón, Eva
Pumarola, Martí
Badiola, Juan José
Bolea, Rosa
Fecha de publicación
2021-03-08ISSN
1661-6596
Resumen
Neurotrophins constitute a group of growth factor that exerts important functions in the nervous system of vertebrates. They act through two classes of transmembrane receptors: tyrosine-kinase receptors and the p75 neurotrophin receptor (p75NTR). The activation of p75NTR can favor cell survival or apoptosis depending on diverse factors. Several studies evidenced a link between p75NTR and the pathogenesis of prion diseases. In this study, we investigated the distribution of several neurotrophins and their receptors, including p75NTR, in the brain of naturally scrapie-affected sheep and experimentally infected ovinized transgenic mice and its correlation with other markers of prion disease. No evident changes in infected mice or sheep were observed regarding neurotrophins and their receptors except for the immunohistochemistry against p75NTR. Infected mice showed higher abundance of p75NTR immunostained cells than their non-infected counterparts. The astrocytic labeling correlated with other neuropathological alterations of prion disease. Confocal microscopy demonstrated the co-localization of p75NTR and the astrocytic marker GFAP, suggesting an involvement of astrocytes in p75NTR-mediated neurodegeneration. In contrast, p75NTR staining in sheep lacked astrocytic labeling. However, digital image analyses revealed increased labeling intensities in preclinical sheep compared with non-infected and terminal sheep in several brain nuclei. This suggests that this receptor is overexpressed in early stages of prion-related neurodegeneration in sheep. Our results confirm a role of p75NTR in the pathogenesis of classical ovine scrapie in both the natural host and in an experimental transgenic mouse model.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
619 - Veterinaria
Páginas
18
Publicado por
MDPI
Publicado en
International Journal of Molecular Sciences
Citación
Barrio, Tomás, Enric Vidal, Marina Betancor, Alicia Otero, Inmaculada Martín-Burriel, Marta Monzón, Eva Monleón, Martí Pumarola, Juan José Badiola, and Rosa Bolea. 2021. "Evidence Of P75 Neurotrophin Receptor Involvement In The Central Nervous System Pathogenesis Of Classical Scrapie In Sheep And A Transgenic Mouse Model". International Journal Of Molecular Sciences 22 (5): 2714. doi:10.3390/ijms22052714.
Número del acuerdo de la subvención
MINECO/Programa Estatal de I + D + I orientada a los retos de la sociedad/AGL2015-65560-R/ES/Implicación de la glicosilación en la transmisión de las enfermedades priónicas, biomarcadores moleculares y papel de las neurotrofinas en la neurodegeneración/
Program
Sanitat Animal
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