Altered transition metal homeostasis in the cuprizone model of demyelination.
In the cuprizone model of demyelination, the neurotoxin cuprizone is fed to mice to induce a reproducible pattern of demyelination in the brain. Cuprizone is a copper chelator and it has been hypothesized that it induces a copper deficiency in the brain, which leads to demyelination. To test this hypothesis and investigate the possible role of other transition metals in the model, we fed C57Bl/6 mice a standard dose of cuprizone (0.2% dry chemical to dry food weight) for 6 weeks then measured levels of copper, manganese, iron, and zinc in regions of the brain and visceral organs. As expected, this treatment induced demyelination in the mice. We found, however, that while the treatment significantly reduced copper concentrations in the blood and liver in treated animals, there was no significant difference in concentrations in brain regions relative to control. Interestingly, cuprizone disrupted concentrations of the other transition metals in the visceral organs, with the most notable changes being decreased manganese and increased iron in the liver. In the brain, manganese concentrations were also significantly reduced in the cerebellum and striatum. These data suggest a possible role of manganese deficiency in the brain in the cuprizone model.
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.
Nataliya
N
Moldovan
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.
Alia
A
Al-Ebraheem
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.
Lianne
L
Lobo
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.
Raina
R
Park
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.
Michael J
MJ
Farquharson
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada. Electronic address: bockn@mcmaster.ca.
Nicholas A
NA
Bock
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002614:Chelating Agents; D003300:Copper / Q000097:blood / Q000378:metabolism*; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D015032:Zinc / Q000378:metabolism
D002614:Chelating Agents; D008345:Manganese; D003471:Cuprizone; D003300:Copper; D007501:Iron; D015032:Zinc
C57Bl/6 mice; Cuprizone model; Demyelination; Neutron activation analysis (NAA); Transition metals; X-ray fluorescence (XRF)