Chronic exposure to high levels of zinc or copper has little effect on brain metal homeostasis or Abeta accumulation in transgenic APP-C100 mice

Aberrant metal homeostasis may enhance the formation of reactive oxygen species and Abeta oligomerization and may therefore be a contributing factor in Alzheimer's disease. This study investigated the effect of chronic high intake of dietary Zn or Cu on brain metal levels and the accumulation a...

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Bibliographic Details
Published in:Cellular and molecular neurobiology 2009-07, Vol.29 (5), p.757
Main Authors: Maynard, Christa J, Cappai, Roberto, Volitakis, Irene, Laughton, Katrina M, Masters, Colin L, Bush, Ashley I, Li, Qiao-Xin
Format: Article
Language:English
Subjects:
Amyloid beta-Protein Precursor - metabolism
Animals
Biomarkers - metabolism
Brain - cytology
Brain - drug effects
Brain - metabolism
Copper - administration & dosage
Copper - toxicity
Diet
Drinking - drug effects
Environmental Exposure
Enzyme-Linked Immunosorbent Assay
Feeding Behavior - drug effects
Glial Fibrillary Acidic Protein - metabolism
Homeostasis - drug effects
Humans
Immunohistochemistry
Mice
Mice, Transgenic
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Stress, Physiological - drug effects
Zinc - administration & dosage
Zinc - toxicity
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Summary:Aberrant metal homeostasis may enhance the formation of reactive oxygen species and Abeta oligomerization and may therefore be a contributing factor in Alzheimer's disease. This study investigated the effect of chronic high intake of dietary Zn or Cu on brain metal levels and the accumulation and solubility of Abeta in vivo, using a transgenic mouse model that over expresses the C-terminal containing Abeta fragment of human amyloid precursor protein but does not develop amyloid deposits. Exposure to chronic high Zn or Cu in the drinking water resulted in only slight elevations of the respective metals in the brain. Total Abeta levels were unchanged although soluble Abeta levels were slightly decreased, without visible plaque formation, enhanced gliosis, antioxidant upregulation or neuronal loss. This study indicates that brain metal levels are only marginally altered by long term oral exposure to extremely high Cu or Zn levels, and that this does not induce Abeta-amyloid formation in human Abeta expressing, amyloid-free mice, although this is sufficient to modulate Abeta solubility in vivo.
ISSN:1573-6830
1573-6830
DOI:10.1007/s10571-009-9401-7