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

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-infec...

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Autores principales: Vascellari, Sarah, Banni, Sebastiano, Vacca, Claudia, Vetrugno, Vito, Cardone, Franco, Di Bari, Michele A, La Colla, Paolo, Pani, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162549/
https://www.ncbi.nlm.nih.gov/pubmed/21816038
http://dx.doi.org/10.1186/1476-511X-10-132
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author Vascellari, Sarah
Banni, Sebastiano
Vacca, Claudia
Vetrugno, Vito
Cardone, Franco
Di Bari, Michele A
La Colla, Paolo
Pani, Alessandra
author_facet Vascellari, Sarah
Banni, Sebastiano
Vacca, Claudia
Vetrugno, Vito
Cardone, Franco
Di Bari, Michele A
La Colla, Paolo
Pani, Alessandra
author_sort Vascellari, Sarah
collection PubMed
description 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. CONCLUSION: 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.
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spelling pubmed-31625492011-08-27 Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains Vascellari, Sarah Banni, Sebastiano Vacca, Claudia Vetrugno, Vito Cardone, Franco Di Bari, Michele A La Colla, Paolo Pani, Alessandra Lipids Health Dis Research 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. CONCLUSION: 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. BioMed Central 2011-08-04 /pmc/articles/PMC3162549/ /pubmed/21816038 http://dx.doi.org/10.1186/1476-511X-10-132 Text en Copyright ©2011 Vascellari et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Vascellari, Sarah
Banni, Sebastiano
Vacca, Claudia
Vetrugno, Vito
Cardone, Franco
Di Bari, Michele A
La Colla, Paolo
Pani, Alessandra
Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162549/
https://www.ncbi.nlm.nih.gov/pubmed/21816038
http://dx.doi.org/10.1186/1476-511X-10-132
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