Dinamica e localizzazione dell'accumulo di proteina prionica patologica (PrPSc) nelle placente di ovini di razza ARQ/ARQ affetti da scrapie naturale e sperimentale

Scrapie is a fatal, neurodegenerative disease of sheep and goats. It belongs to a group of diseases known as transmissible spongiform encephalopathies (TSEs) which are characterized by the accumulation of an abnormal isoform (PrP^Sc) of the host-encoded prion protein (PrP^C) in the brain. In sheep, susceptibility or resistance to scrapie is strongly modulated by the polymorphisms at codons 136, 154 and 171, of the PRNP gene region, which codifies for the C-terminal structured domain of the host-encoded prion protein. A particular important question relates to those factors permitting horizontal transmission of scrapie within sheep flocks. Although the main target of prion-induced pathology is the central nervous system (CNS), PrPSc can be readily demonstrated in extraneuronal tissue, including placenta which may contribute in the horizontal scrapie transmission The aim of this study is to characterize dynamic, cellular localization and genetic aspects of PrPSc deposition in placenta from ARQ/ARQwildtype and ARQ/ARQmutated Sarda breed sheep. To do this placenta and uterus from experimentally and naturally scrapie-affected sheep were screened. By performing western blot and immunohistochemistry 23 clinically healthy scrapie-affected ewes coming from three scrapie outbreaks, 29 clinically scrapie-affected and 11 experimentally scrapieaffected ewes with clinical signs were analyzed. Deposition of PrP^Sc was showed in the placentomes of the ARQ/ARQwildtype sheep, both in the epithelial cells of the endometrial maternal mucosa and in the trophoblastic cells. The localization of PrP^Sc deposits in the placentomes was temporally associated with different stage of gestation. For the first time, it is shown that ARQ/ARQ sheep with foetus carrying the mutations F141L or N176K did not accumulate PrP^Sc in the placenta.