Evidence of p75 Neurotrophin Receptor Involvement in the Central Nervous System Pathogenesis of Classical Scrapie in Sheep and a Transgenic Mouse Model

Neurotrophins constitute a group of growth factor that exerts important functions in the nervous system vertebrates. They act through two classes transmembrane receptors: tyrosine-kinase receptors and p75 neurotrophin receptor (p75NTR). The activation p75NTR can favor cell survival or apoptosis depending on diverse factors. Several studies evidenced link between pathogenesis prion diseases. In this study, we investigated distribution several neurotrophins their receptors, including p75NTR, brain naturally scrapie-affected sheep experimentally infected ovinized transgenic mice its correlation with other markers disease. No evident changes were observed regarding except for immunohistochemistry against p75NTR. Infected showed higher abundance immunostained cells than non-infected counterparts. astrocytic labeling correlated neuropathological alterations Confocal microscopy demonstrated co-localization marker GFAP, suggesting an involvement astrocytes p75NTR-mediated neurodegeneration. contrast, staining lacked labeling. However, digital image analyses revealed increased intensities preclinical compared terminal nuclei. This suggests is overexpressed early stages prion-related neurodegeneration sheep. Our results confirm role classical ovine scrapie both natural host experimental mouse model.