title: Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains.
abstract: OBJECTIVE
  Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial.
  
  
  METHODS
  To shed light on the matter, we analysed and compared cholesterol variations in ScN2a cells and in brains of Scrapie-infected C57Bl/6 mice, using two different methods: a fluorimetric-enzymatic cholesterol assay, and high performance liquid chromatography-mass spectroscopy (HPLC-MS).
  
  
  RESULTS
  Compared to uninfected controls, similar cholesterol metabolism anomalies were observed in infected cells and brains by both methods; however, only HPLC-MS revealed statistically significant cholesterol variations, particularly in the cholesteryl esters (CE) fraction. HPLC-MS analyses also revealed different fatty acid composition of the CE fraction in cells and brains. In N2a cells, their profile reflected that of serum, while in normal brains cholesteryl-linoleate only was found at detectable levels. Following prion infection, most CE species were increased in the CE pool of ScN2a cells, whereas a conspicuous amount of cholesteryl-arachidonate only was found to contribute to the cerebral increase of CE. Of interest, oral pravastatin administration to Scrapie-infected mice, was associated with a significant reduction of cerebral free cholesterol (FC) along with a concomitant further increase of the CE pool, which included increased amounts of both cholesteryl-linoleate and cholesteryl-arachidonate.
  
  
  CONCLUSIONS
  Although mechanistic studies are needed to establish the pathophysiological relevance of changes in cerebral CE concentrations, to the best of our knowledge this is the first report to provide evidence of increased cholesterol esterification in brains of prion-infected mice, untreated and treated with pravastatin.
authors.affiliation: Department of Biomedical Science and Technology, University of Cagliari, 09042-Monserrato, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vascellari
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Banni
authors.forename: Claudia
authors.initials: C
authors.lastname: Vacca
authors.forename: Vito
authors.initials: V
authors.lastname: Vetrugno
authors.forename: Franco
authors.initials: F
authors.lastname: Cardone
authors.forename: Michele A
authors.initials: MA
authors.lastname: Di Bari
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pani
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D010078:Oxazines / Q000737:chemistry; D017035:Pravastatin / Q000494:pharmacology; D012608:Scrapie / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D002788:Cholesterol Esters; D005227:Fatty Acids; D010078:Oxazines; C470430:Amplex Red; D017035:Pravastatin