Evidence for decreased copper associated with demyelination in the corpus callosum of cuprizone-treated mice.
Hilton, JBW
Kysenius, K
Liddell, JR
Mercer, SW
Hare, DJ
Buncic, G
Paul, B
Wang, Y
Murray, SS
Kilpatrick, TJ
White, AR
Donnelly, PS
Crouch, PJ
- Publisher:
- Oxford University Press (OUP)
- Publication Type:
- Journal Article
- Citation:
- Metallomics, 2024, 16, (1), pp. mfad072
- Issue Date:
- 2024-01-05
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Hilton, JBW | |
dc.contributor.author | Kysenius, K | |
dc.contributor.author | Liddell, JR | |
dc.contributor.author | Mercer, SW | |
dc.contributor.author | Hare, DJ | |
dc.contributor.author | Buncic, G | |
dc.contributor.author | Paul, B | |
dc.contributor.author | Wang, Y | |
dc.contributor.author | Murray, SS | |
dc.contributor.author | Kilpatrick, TJ | |
dc.contributor.author | White, AR | |
dc.contributor.author | Donnelly, PS | |
dc.contributor.author | Crouch, PJ | |
dc.date.accessioned | 2024-08-06T02:12:04Z | |
dc.date.available | 2023-11-24 | |
dc.date.available | 2024-08-06T02:12:04Z | |
dc.date.issued | 2024-01-05 | |
dc.identifier.citation | Metallomics, 2024, 16, (1), pp. mfad072 | |
dc.identifier.issn | 1756-5901 | |
dc.identifier.issn | 1756-591X | |
dc.identifier.uri | http://hdl.handle.net/10453/180066 | |
dc.description.abstract | Demyelination within the central nervous system (CNS) is a significant feature of debilitating neurological diseases such as multiple sclerosis and administering the copper-selective chelatorcuprizone to mice is widely used to model demyelination in vivo. Conspicuous demyelination within the corpus callosum is generally attributed to cuprizone's ability to restrict copper availability in this vulnerable brain region. However, the small number of studies that have assessed copper in brain tissue from cuprizone-treated mice have produced seemingly conflicting outcomes, leaving the role of CNS copper availability in demyelination unresolved. Herein we describe our assessment of copper concentrations in brain samples from mice treated with cuprizone for 40 d. Importantly, we applied an inductively coupled plasma mass spectrometry methodology that enabled assessment of copper partitioned into soluble and insoluble fractions within distinct brain regions, including the corpus callosum. Our results show that cuprizone-induced demyelination in the corpus callosum was associated with decreased soluble copper in this brain region. Insoluble copper in the corpus callosum was unaffected, as were pools of soluble and insoluble copper in other brain regions. Treatment with the blood-brain barrier permeant copper compound CuII(atsm) increased brain copper levels and this was most pronounced in the soluble fraction of the corpus callosum. This effect was associated with significant mitigation of cuprizone-induced demyelination. These results provide support for the involvement of decreased CNS copper availability in demyelination in the cuprizone model. Relevance to human demyelinating disease is discussed. | |
dc.format | ||
dc.language | eng | |
dc.publisher | Oxford University Press (OUP) | |
dc.relation.ispartof | Metallomics | |
dc.relation.isbasedon | 10.1093/mtomcs/mfad072 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 03 Chemical Sciences | |
dc.subject.classification | Analytical Chemistry | |
dc.subject.classification | 34 Chemical sciences | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Cuprizone | |
dc.subject.mesh | Corpus Callosum | |
dc.subject.mesh | Demyelinating Diseases | |
dc.subject.mesh | Copper | |
dc.subject.mesh | Oligodendroglia | |
dc.subject.mesh | Mice, Inbred C57BL | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Myelin Sheath | |
dc.subject.mesh | Corpus Callosum | |
dc.subject.mesh | Oligodendroglia | |
dc.subject.mesh | Myelin Sheath | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Mice, Inbred C57BL | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Demyelinating Diseases | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Copper | |
dc.subject.mesh | Cuprizone | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Cuprizone | |
dc.subject.mesh | Corpus Callosum | |
dc.subject.mesh | Demyelinating Diseases | |
dc.subject.mesh | Copper | |
dc.subject.mesh | Oligodendroglia | |
dc.subject.mesh | Mice, Inbred C57BL | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Myelin Sheath | |
dc.title | Evidence for decreased copper associated with demyelination in the corpus callosum of cuprizone-treated mice. | |
dc.type | Journal Article | |
utslib.citation.volume | 16 | |
utslib.location.activity | England | |
utslib.for | 03 Chemical Sciences | |
pubs.organisational-group | University of Technology Sydney | |
pubs.organisational-group | University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
utslib.copyright.status | open_access | * |
dc.rights.license | This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ | |
dc.date.updated | 2024-08-06T02:12:01Z | |
pubs.issue | 1 | |
pubs.publication-status | Published | |
pubs.volume | 16 | |
utslib.citation.issue | 1 |
Abstract:
Demyelination within the central nervous system (CNS) is a significant feature of debilitating neurological diseases such as multiple sclerosis and administering the copper-selective chelatorcuprizone to mice is widely used to model demyelination in vivo. Conspicuous demyelination within the corpus callosum is generally attributed to cuprizone's ability to restrict copper availability in this vulnerable brain region. However, the small number of studies that have assessed copper in brain tissue from cuprizone-treated mice have produced seemingly conflicting outcomes, leaving the role of CNS copper availability in demyelination unresolved. Herein we describe our assessment of copper concentrations in brain samples from mice treated with cuprizone for 40 d. Importantly, we applied an inductively coupled plasma mass spectrometry methodology that enabled assessment of copper partitioned into soluble and insoluble fractions within distinct brain regions, including the corpus callosum. Our results show that cuprizone-induced demyelination in the corpus callosum was associated with decreased soluble copper in this brain region. Insoluble copper in the corpus callosum was unaffected, as were pools of soluble and insoluble copper in other brain regions. Treatment with the blood-brain barrier permeant copper compound CuII(atsm) increased brain copper levels and this was most pronounced in the soluble fraction of the corpus callosum. This effect was associated with significant mitigation of cuprizone-induced demyelination. These results provide support for the involvement of decreased CNS copper availability in demyelination in the cuprizone model. Relevance to human demyelinating disease is discussed.
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