Evidence for decreased copper associated with demyelination in the corpus callosum of cuprizone-treated mice

被引：7

作者：

Hilton, James B. W. ^{[1
]}

Kysenius, Kai ^{[1
,2
]}

Liddell, Jeffrey R. ^{[1
]}

Mercer, Stephen W. ^{[1
]}

Hare, Dominic J. ^{[3
]}

Buncic, Gojko ^{[4
,5
]}

Paul, Bence ^{[6
]}

Wang, Youjia ^{[1
]}

Murray, Simon S. ^{[1
,2
]}

Kilpatrick, Trevor J. ^{[1
,2
]}

White, Anthony R. ^{[7
]}

Donnelly, Paul S. ^{[4
,5
]}

Crouch, Peter J. ^{[1
]}

机构：

[1] Univ Melbourne, Dept Anat & Physiol, Melbourne, Vic 3010, Australia

[2] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic 3010, Australia

[3] Univ Technol Sydney, Atom Med Initiat, Sydney, NSW 2007, Australia

[4] Univ Melbourne, Sch Chem, Melbourne, Vic 3010, Australia

[5] Univ Melbourne, Bio21 Mol Sci & Biotechnol Inst, Melbourne, Vic 3010, Australia

[6] Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia

[7] Queensland Inst Med Res Berghofer, Herston, Qld 4006, Australia

来源：

METALLOMICS | 2024年 / 16卷 / 01期

关键词：

copper; corpus callosum; cuprizone; multiple sclerosis; demyelination; Cu(atsm); myelin; protection; therapy; OXIDATIVE STRESS; MOUSE-BRAIN; CU-ATSM; MODEL; DISEASE; DEFICIENCY; MOTOR; REMYELINATION; MYELINATION; CU-II(ATSM);

D O I：

10.1093/mtomcs/mfad072

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. Graphical Abstract Cuprizone-induced demyelination in the mouse corpus callosum involves depletion of copper in the soluble fraction of this vulnerable brain region. Pharmacological copper delivery to the brain is protective.

引用

页数：10

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