2004 Denver Annual Meeting (November 7–10, 2004)

Paper No. 11
Presentation Time: 11:00 AM


JONES, Blair F., US Geol Survey, 432 National Ctr, Reston, VA 20192-0001, bfjones@usgs.gov

A number of metals in relatively low concentration have been identified as essential to human health. Concern has been raised about the effects of deficiency in these elements, particularly with respect to metabolic catalysis, oxygen binding and transport, and hormonal functions, but little study of the effects of excesses has been undertaken. Recent investigations have highlighted the participation of minor metals in oxidative damage of vital organs. Metal-protein interactions, especially redox reactions involving Fe, Cu, and Zn, appear to play a key role in these processes. An example is a leading theory of the cause of Alzheimer’s disease (AD), which is characterized by the presence of plaques composed of amyloid protein. The amyloid is initially produced in soluble form, but is aggregated by Zn at normal pH, or Fe and Cu under slightly more acid conditions. Reduction of Cu2+ and Fe3+ by soluble amyloid can generate reduced oxygen species (ROS, e.g. H2O2), probably responsible for brain damage in AD (Bush & Tanzi, 2002). The ROS also interfere with the uptake of synaptic zinc, and the excess Zn not only causes aggregation of the amyloid, but itself causes neuronal damage. Aggregation of amyloid into plaques may reduce its toxicity (Cuajungco et al., 2000). Our research has focused on the cognitive effects of relatively long-term exposure to enhanced levels of Zn, Fe, and Cu and their natural associations in drinking water. Before starting our experiments, we were warned that buffer mechanisms would preclude adding zinc in the brain by simple ingestion, but we have demonstrated in rats both increased levels of Zn in the cortex and hippocampus by synchrotron x-ray fluorescence (also Fe and Cu), and deficits in spatial memory with the Morris Water Maze. In addition, these results were dependent on the major anion association with the metal; ZnCO3 showed the most effect, ZnSO4 almost none, and ZnCl2 was intermediate. The differences due to anion association were greater than those due to dose in the 5-40 ppm Zn range. Experiments with wild type and transgenic mice have confirmed cognitive impairment associated with ingestion of zinc, and showed deficits in transgenic mice drinking iron-bearing water of similar concentration. Further experiments are in process.