Evidence of p75 Neurotrophin Receptor Involvement in the Central Nervous System Pathogenesis of Classical Scrapie in Sheep and a Transgenic Mouse Model
Barrio, Tomás (Universidad de Zaragoza. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes)
Vidal Barba, Enric (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Betancor, Marina (Universidad de Zaragoza. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes)
Otero García, Alicia (Universidad de Zaragoza. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes)
Martín-Burriel, Inmaculada (Instituto Agroalimentario de Aragón. Laboratorio de Genética Bioquímica)
Monzón, Marta (Universidad de Zaragoza. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes)
Monleón, Eva (Universidad de Zaragoza. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes)
Pumarola i Batlle, Martí (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Badiola, Juan José (Universidad de Zaragoza. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes)

Date:	2021
Abstract:	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 (p75 NTR). The activation of p75 NTR can favor cell survival or apoptosis depending on diverse factors. Several studies evidenced a link between p75 NTR and the pathogenesis of prion diseases. In this study, we investigated the distribution of several neurotrophins and their receptors, including p75 NTR, 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 p75 NTR. Infected mice showed higher abundance of p75 NTR 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 p75 NTR and the astrocytic marker GFAP, suggesting an involvement of astrocytes in p75 NTR -mediated neurodegeneration. In contrast, p75 NTR 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 p75 NTR in the pathogenesis of classical ovine scrapie in both the natural host and in an experimental transgenic mouse model.
Grants:	Ministerio de Economía y Competitividad AGL2015-65560-R Ministerio de Economía y Competitividad FPU14/04348
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Prion disease ; Scrapie ; Neurotrophin ; P75 NTR ; Astrocyte ; Transgenic mice
Published in:	International journal of molecular sciences, Vol. 22 (march 2021) , ISSN 1422-0067

DOI: 10.3390/ijms22052714
PMID: 33800240

18 p, 28.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
Articles > Research articles
Articles > Published articles