Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains

<p>Abstract</p> <p>Objective</p> <p>Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial.</p> <p>Methods</p> <p>To shed light on the matter, w...

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Main Authors: Di Bari Michele A, Cardone Franco, Vetrugno Vito, Vacca Claudia, Banni Sebastiano, Vascellari Sarah, La Colla Paolo, Pani Alessandra
Format: Article
Language:English
Published: BMC 2011-08-01
Series:Lipids in Health and Disease
Subjects:
Online Access:http://www.lipidworld.com/content/10/1/132
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author Di Bari Michele A
Cardone Franco
Vetrugno Vito
Vacca Claudia
Banni Sebastiano
Vascellari Sarah
La Colla Paolo
Pani Alessandra
author_facet Di Bari Michele A
Cardone Franco
Vetrugno Vito
Vacca Claudia
Banni Sebastiano
Vascellari Sarah
La Colla Paolo
Pani Alessandra
author_sort Di Bari Michele A
collection DOAJ
description <p>Abstract</p> <p>Objective</p> <p>Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-31821da1378e4ab099628544eccb70b72022-12-22T02:46:08ZengBMCLipids in Health and Disease1476-511X2011-08-0110113210.1186/1476-511X-10-132Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brainsDi Bari Michele ACardone FrancoVetrugno VitoVacca ClaudiaBanni SebastianoVascellari SarahLa Colla PaoloPani Alessandra<p>Abstract</p> <p>Objective</p> <p>Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>http://www.lipidworld.com/content/10/1/132PrionsCholesterolCholesteryl estersFatty acidsStatins
spellingShingle Di Bari Michele A
Cardone Franco
Vetrugno Vito
Vacca Claudia
Banni Sebastiano
Vascellari Sarah
La Colla Paolo
Pani Alessandra
Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
Lipids in Health and Disease
Prions
Cholesterol
Cholesteryl esters
Fatty acids
Statins
title Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
title_full Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
title_fullStr Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
title_full_unstemmed Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
title_short Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
title_sort accumulation and aberrant composition of cholesteryl esters in scrapie infected n2a cells and c57bl 6 mouse brains
topic Prions
Cholesterol
Cholesteryl esters
Fatty acids
Statins
url http://www.lipidworld.com/content/10/1/132
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