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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\u2013brain 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.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfad072","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T07:09:41Z","timestamp":1704438581000},"source":"Crossref","is-referenced-by-count":14,"title":["Evidence for decreased copper associated with demyelination in the corpus callosum of cuprizone-treated mice"],"prefix":"10.1093","volume":"16","author":[{"given":"James B W","family":"Hilton","sequence":"first","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kysenius","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"},{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R","family":"Liddell","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W","family":"Mercer","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic J","family":"Hare","sequence":"additional","affiliation":[{"name":"Atomic Medicine Initiative, University of Technology Sydney , Sydney, New South Wales 2007 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gojko","family":"Buncic","sequence":"additional","affiliation":[{"name":"School of Chemistry and Bio21 Molecular Science and Biotechnology Institute , T , Victoria 3010 , Australia"},{"name":"he University of Melbourne , T , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Paul","sequence":"additional","affiliation":[{"name":"School of Earth Sciences, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YouJia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon S","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"},{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor J","family":"Kilpatrick","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"},{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R","family":"White","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research Berghofer , Herston, Queensland 4006 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S","family":"Donnelly","sequence":"additional","affiliation":[{"name":"School of Chemistry and Bio21 Molecular Science and Biotechnology Institute , , Victoria 3010 , Australia"},{"name":"The University of Melbourne , , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Crouch","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne , Victoria 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"key":"2024011909265276200_bib1","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1007\/978-1-4614-1533-6_128","volume-title":"Encyclopedia of Metalloproteins","author":"Harris","year":"2013"},{"issue":"5","key":"2024011909265276200_bib2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/ejhg.2009.187","article-title":"Menkes Disease","volume":"18","author":"Tumer","year":"2010","journal-title":"Eur. 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