title: Lipid profiles in brains from sheep with natural scrapie.
abstract: Prion diseases are fatal neurodegenerative disorders affecting many mammals, ovine scrapie being the archetypal prion disease. Several independent studies in murine and cell-based models of scrapie have highlighted the presence of a link between prion generation and lipid alterations; yet, no data on natural disease are available. In this study we investigated levels of total lipids and cholesterol as well as profiles of fatty acids in brain homogenates from symptomatic and asymptomatic scrapie-infected sheep vs. healthy sheep, all belonging to the same flock. Lipid extracts were analyzed by means of gas chromatography and high performance liquid chromatography. Data of fatty acids were submitted to multivariate statistical analysis to give a picture of the brain lipid profiles of sheep. Interestingly, results revealed abnormalities in the brain fatty acid unsaturation of infected/symptomatic animals. Significant reduction of monoene 18:1 n-9 was detected in brain lipids from infected/symptomatic sheep, as compared to healthy and infected/asymptomatic animals, and this alteration occurred in combination with a significant increase in 18:0 level. The unsupervised Principal Component Analysis showed that infected/symptomatic and healthy sheep samples lie in two different regions of the plot, infected/asymptomatic lie mostly next to healthy. The increase of cerebral saturated fatty acids provides a rough indication of presumed alterations in lipid raft domains of nervous cells during scrapie, suggesting that they may exist in a notable viscous liquid-ordered state. Such physicochemical alteration would have a profound impact on the raft thermodynamic properties, its spatial organization, and signal transduction, all potentially relevant for prion generation.
authors: Department of Biomedical Sciences, University of Cagliari, Monserrato 09042, Italy. Electronic address: anrosa@unica.it.
authors: Antonella
authors: A
authors: Rosa
authors: Paola
authors: P
authors: Scano
authors: Alessandra
authors: A
authors: Incani
authors: Federica
authors: F
authors: Pilla
authors: Caterina
authors: C
authors: Maestrale
authors: Matteo
authors: M
authors: Manca
authors: Ciriaco
authors: C
authors: Ligios
authors: Alessandra
authors: A
authors: Pani
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005227:Fatty Acids / Q000032:analysis* / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology*; D012756:Sheep
chemical_list: D005227:Fatty Acids; D008055:Lipids
keywords: Brain lipid composition; Fatty acid profile; Prion disease; Scrapie