Abstract
One common characteristic of neurodegenerative diseases is dysregulation of iron, usually with observed increases in its concentration in various regions. Heavy alcohol consumption is believed to contribute to such iron dysregulation in the brain with accompanying dementia. To examine this effect and related genetic-based individual differences in an animal model, we subjected female mice from 12 BXD recombinant inbred strains to 16 weeks of alcohol consumption using the drinking in the dark (DID) method. Daily consumption was recorded and at the end of 16 weeks hippocampus tissues harvested. Concentrations of iron, copper and zinc were measured using X-ray fluorescence technology. The results showed that, DID increased iron overall across all strains, ranging from 3 to 68%. Copper and Zinc both decreased, ranging from 0.4–42 and 5–35% respectively. Analysis of variance revealed significant strain by treatment interactions for all three metals. Additionally, in the DID group, we observed strain differences in reduction of hippocampus mass. These findings are particularly interesting to us because high alcohol consumption in humans has been associated with neurodegeneration and dementia related to disruption of iron regulation. The findings of alcohol consumption associated decreases in copper and zinc are novel. The role of copper regulation and neurological function related to alcohol consumption is as yet largely unexplored. The role of zinc is better known as a neuromodulator in the hippocampus and appears to be protective against neurological damage. It would seem then, that the alcohol-related decrease in zinc in the hippocampus would be of concern and warrants further study.
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This study was supported in part by USPHS Grant R01AA021951.
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BCJ and MKM; designed study and wrote main text: KME, LL, and RWW: edited text: WZ, DZ and CT-R performed DID, conducted the metals analysis, ran statistical analyses and produced graphs.
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All procedures using live mice were approved by the UTHSC Institutional Animal Care and Use Committee.
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Jones, B.C., Erikson, K.M., Mulligan, M.K. et al. Genetic differences in ethanol consumption: effects on iron, copper, and zinc regulation in mouse hippocampus. Biometals 34, 1059–1066 (2021). https://doi.org/10.1007/s10534-021-00327-8
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DOI: https://doi.org/10.1007/s10534-021-00327-8