The Effects That Dietary Manipulations of Zinc and Copper Have on Nest Building, Zinc Transporter and Glial Fibrillary Acidic Protein Expression in a Transgenic Mouse Model of Alzheimer’s Disease

Abstract

The role of essential trace elements, such as zinc and copper, in Alzheimer’s disease (AD) has received much attention in the last decade. Zinc (Zn) and copper (Cu) are involved in many biological processes. Amyloid-β (Aβ) interacts with these metal ions, sequesters them, and causes an intracellular decrease in Zn and Cu. In this study, we characterize nest building ability, zinc transporter 3 (ZnT3) and glial fibrillary acidic protein (GFAP) expression in wildtype (WT) and transgenic (J20) mice in one of three dietary conditions: regular lab water (LW) with a copper-control (CC) diet (LW/CC); regular LW with a copper-deficient (CD) diet (LW/CD); or lab water enhanced with 10 ppm ZnCO3 with the CC diet (Zn/CC). Based on previous work from our laboratory, Zn-enhanced water was shown to induce behavioral deficits, but when Cu was added to the Zn drinking water, the behavioral deficits were abrogated. Other studies however have shown that Cu-deficiency may be beneficial in AD. We sought out to evaluate what mechanisms may be involved in Zn supplementation and whether or not there would be similar results between the two manipulated diets. Surprisingly, J20 mice significantly outperformed WT mice in the nesting assay, but in only the LW/CC condition. Males outperformed females on the nesting assay, but again this was significant in only the LW/CC group (p<.05). ZnT3 levels were not observed to be different based on genotype, but diet did induce higher expression of ZnT3 (p<.10), with the Zn/CC group expressing the highest and the control LW/CC group expressing the least amount (p<.05). GFAP levels were less consistent but the manipulated diets induced higher expression of GFAP (p < .10). Also, the only genotypic difference was observed in the control LW/CC which shows that the manipulated diets made the WT mice take on a J20 profile. These data warrant further investigation into the role of dietary Zn and Cu therapeutics.