Cuprizone feed formulation influences the extent of demyelinating disease pathology

Abstract Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-c...

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Autores principales:	Lillian M. Toomey, Melissa Papini, Brittney Lins, Alexander J. Wright, Andrew Warnock, Terence McGonigle, Sarah C. Hellewell, Carole A. Bartlett, Chidozie Anyaegbu, Melinda Fitzgerald
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/580b3adbc43c41d781115c06f9481e95
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spelling	oai:doaj.org-article:580b3adbc43c41d781115c06f9481e952021-11-21T12:17:44ZCuprizone feed formulation influences the extent of demyelinating disease pathology10.1038/s41598-021-01963-32045-2322https://doaj.org/article/580b3adbc43c41d781115c06f9481e952021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01963-3https://doaj.org/toc/2045-2322Abstract Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering cuprizone, but the efficacy of these pellets at inducing demyelination has been questioned. This study compared the degree of demyelinating disease pathology between mice fed cuprizone delivered in pellets to mice fed a powdered cuprizone formulation at an early 3 week demyelinating timepoint. Within rostral corpus callosum, cuprizone pellets were more effective than cuprizone powder at increasing astrogliosis, microglial activation, DNA damage, and decreasing the density of mature oligodendrocytes. However, cuprizone powder demonstrated greater protein nitration relative to controls. Furthermore, mice fed control powder had significantly fewer mature oligodendrocytes than those fed control pellets. In caudal corpus callosum, cuprizone pellets performed better than cuprizone powder relative to controls at increasing astrogliosis, microglial activation, protein nitration, DNA damage, tissue swelling, and reducing the density of mature oligodendrocytes. Importantly, only cuprizone pellets induced detectable demyelination compared to controls. The two feeds had similar effects on oligodendrocyte precursor cell (OPC) dynamics. Taken together, these data suggest that demyelinating disease pathology is modelled more effectively with cuprizone pellets than powder at 3 weeks. Combined with the added convenience, cuprizone pellets are a suitable choice for inducing early demyelinating disease pathology.Lillian M. ToomeyMelissa PapiniBrittney LinsAlexander J. WrightAndrew WarnockTerence McGonigleSarah C. HellewellCarole A. BartlettChidozie AnyaegbuMelinda FitzgeraldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lillian M. Toomey Melissa Papini Brittney Lins Alexander J. Wright Andrew Warnock Terence McGonigle Sarah C. Hellewell Carole A. Bartlett Chidozie Anyaegbu Melinda Fitzgerald Cuprizone feed formulation influences the extent of demyelinating disease pathology
description	Abstract Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering cuprizone, but the efficacy of these pellets at inducing demyelination has been questioned. This study compared the degree of demyelinating disease pathology between mice fed cuprizone delivered in pellets to mice fed a powdered cuprizone formulation at an early 3 week demyelinating timepoint. Within rostral corpus callosum, cuprizone pellets were more effective than cuprizone powder at increasing astrogliosis, microglial activation, DNA damage, and decreasing the density of mature oligodendrocytes. However, cuprizone powder demonstrated greater protein nitration relative to controls. Furthermore, mice fed control powder had significantly fewer mature oligodendrocytes than those fed control pellets. In caudal corpus callosum, cuprizone pellets performed better than cuprizone powder relative to controls at increasing astrogliosis, microglial activation, protein nitration, DNA damage, tissue swelling, and reducing the density of mature oligodendrocytes. Importantly, only cuprizone pellets induced detectable demyelination compared to controls. The two feeds had similar effects on oligodendrocyte precursor cell (OPC) dynamics. Taken together, these data suggest that demyelinating disease pathology is modelled more effectively with cuprizone pellets than powder at 3 weeks. Combined with the added convenience, cuprizone pellets are a suitable choice for inducing early demyelinating disease pathology.
format	article
author	Lillian M. Toomey Melissa Papini Brittney Lins Alexander J. Wright Andrew Warnock Terence McGonigle Sarah C. Hellewell Carole A. Bartlett Chidozie Anyaegbu Melinda Fitzgerald
author_facet	Lillian M. Toomey Melissa Papini Brittney Lins Alexander J. Wright Andrew Warnock Terence McGonigle Sarah C. Hellewell Carole A. Bartlett Chidozie Anyaegbu Melinda Fitzgerald
author_sort	Lillian M. Toomey
title	Cuprizone feed formulation influences the extent of demyelinating disease pathology
title_short	Cuprizone feed formulation influences the extent of demyelinating disease pathology
title_full	Cuprizone feed formulation influences the extent of demyelinating disease pathology
title_fullStr	Cuprizone feed formulation influences the extent of demyelinating disease pathology
title_full_unstemmed	Cuprizone feed formulation influences the extent of demyelinating disease pathology
title_sort	cuprizone feed formulation influences the extent of demyelinating disease pathology
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/580b3adbc43c41d781115c06f9481e95
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Cuprizone feed formulation influences the extent of demyelinating disease pathology

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