Biochemical and molecular modifications in sheep brains during natural scrapie

Background. The success in the control of prion disorders depends on both availability of methods for the early detection of prions in biological fluids and identification of factors that favour prion formation in the brain. Recently, we reported that Scrapie-infected mouse brains have increased content of free cholesterol and of the cholesteryl arachidonate fraction of the cholesterol ester pool (Vascellari et al, Lipids Health Dis 2011). Methods. To ascertain presence and relevance of above modifications in natural scrapie, we investigated variations of lipids, and other classes of molecules, in brains of uninfected and scrapie-infected sheep coming from one farm hit by natural scrapie. Of 18 sheep, 7 were healthy and prion-negative (controls); 3 were healthy and prion-positive (asymptomatic scrapie); and 8 were prion-positive with clinical scrapie (symptomatic scrapie). We used biochemical and molecular methods to identify and measure variations in cerebral cholesterols, lipids, and cholesterol-related proteins and genes. Data were integrated and submitted to multivariate statistical analysis. Results and Conclusions. Holistic pictures of the molecular profile of infected vs. uninfected and symptomatic vs. asymptomatic sheep brains will be presented and discussed.