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 \nknown as transmissible spongiform encephalopathies (TSEs) which are characterized by the \naccumulation of an abnormal isoform (PrPSc) of the host-encoded prion protein (PrPC) in the brain. \nIn sheep, susceptibility or resistance to scrapie is strongly modulated by the polymorphisms at \ncodons 136, 154 and 171, of the PRNP gene region, which codifies for the C-terminal structured \ndomain of the host-encoded prion protein. \nA particular important question relates to those factors permitting horizontal transmission of scrapie \nwithin sheep flocks. Although the main target of prion-induced pathology is the central nervous \nsystem (CNS), PrPSc can be readily demonstrated in extraneuronal tissue, including placenta which \nmay contribute in the horizontal scrapie transmission \nThe aim of this study is to characterize dynamic, cellular localization and genetic aspects of PrPSc \ndeposition in placenta from ARQ/ARQwildtype and ARQ/ARQmutated Sarda breed sheep. To do this \nplacenta and uterus from experimentally and naturally scrapie-affected sheep were screened. \nBy performing western blot and immunohistochemistry 23 clinically healthy scrapie-affected ewes \ncoming from three scrapie outbreaks, 29 clinically scrapie-affected and 11 experimentally scrapieaffected \newes with clinical signs were analyzed. \nDeposition of PrPSc was showed in the placentomes of the ARQ/ARQwildtype sheep, both in the \nepithelial cells of the endometrial maternal mucosa and in the trophoblastic cells. The localization \nof PrPSc deposits in the placentomes was temporally associated with different stage of gestation. For \nthe first time, it is shown that ARQ/ARQ sheep with foetus carrying the mutations F141L or \nN176K did not accumulate PrPSc in the placenta.