102172 20230519145441.0 doi 10.3390/ijms22052714 sideral 124123 ART-2021-124123 eng Barrio, Tomás (orcid)0000-0002-7037-6316 Evidence of p75 neurotrophin receptor involvement in the central nervous system pathogenesis of classical scrapie in sheep and a transgenic mouse model 2021 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/MEC/FPU14-04348 info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65560-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 6.208 2021 BIOCHEMISTRY & MOLECULAR BIOLOGY 69 / 297 = 0.232 2021 Q1 T1 CHEMISTRY, MULTIDISCIPLINARY 50 / 180 = 0.278 2021 Q2 T1 1.176 2021 Computer Science Applications 2021 Q1 Inorganic Chemistry 2021 Q1 Spectroscopy 2021 Q1 Organic Chemistry 2021 Q1 Physical and Theoretical Chemistry 2021 Q1 Molecular Biology 2021 Q1 6.9 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Vidal, Enric Betancor, Marina Universidad de Zaragoza (orcid)0000-0002-0388-9429 Otero, Alicia Universidad de Zaragoza (orcid)0000-0001-9075-2764 Martín-Burriel, Inmaculada Universidad de Zaragoza (orcid)0000-0001-6016-4726 Monzón, Marta Universidad de Zaragoza (orcid)0000-0002-2787-9671 Monleón, Eva Universidad de Zaragoza (orcid)0000-0002-7453-1766 Pumarola, Martí Badiola, Juan José Universidad de Zaragoza (orcid)0000-0002-7173-7216 Bolea, Rosa Universidad de Zaragoza (orcid)0000-0002-2746-3932 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 22, 5 (2021), 2714 [18 pp.] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 740968 http://zaguan.unizar.es/record/102172/files/texto_completo.pdf Versión publicada 2849075 http://zaguan.unizar.es/record/102172/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:102172 articulos driver 2023-05-18-14:33:08 ARTICLE