Metals and Neurotoxicology

Metals are ubiquitous and play a critical role in neurobiology. Transition metals are important because they alter the redox state of the physical environment. Biologically, transition metals catalyze redox reactions that are critical to cellular res-piration, chemical detoxification, metabolism, and even neurotransmitter synthesis. Many metals are both nutrients and neurotoxicants, such as iron, zinc, copper, and manganese. Other metals, such as lead and cadmium, are metabolized similarly to these metals, particularly iron. Iron metabolism and genes that regulate iron metabolism may be the key to understanding metal toxicity. Finally, recent evidence demonstrates that early life exposures may program later life and adult disease phenotypes via processes of epigenetics. Parallel work in metals demonstrates that epigenetics may be a critical pathway by which metals produce health effects. J. Nutr. 137: 2809–2813, 2007.

The biological effects of metals are linked to their chemical prop-erties. Transition metals (such as Cu, Fe, and Mn) are particularly adept at catalyzing redox reactions within biological systems. Zn is a nutrient metal that in high dosage can paradoxically promote oxidative toxicity. Heavy metals (Pb, Cd) and metal-loids (As) can also induce oxidative toxicity but more likely work by binding to proteins and interfering with metal transport and protein function. Although Pb and methylmercury neuro-toxicity is well established, the effects of other metals on brain development have only recently drawn attention. Unfortunately, it appears that excess metal exposure may be a common source. of neurotoxicity in multiple populations around the world. Although metals have multiple effects on biological systems, an understudied effect is their role in programming gene ex-pression. A growing body of evidence suggests that metals may influence epigenetic phenomena which regulate the expression of genes and ultimately their protein products. In this article, we focus on the neurotoxic properties of metals and their ability to mimic the pathways of Fe metabolism. In addition, we review the data on the effects of metals on DNA methylation and discuss how these properties might explain fetal origins of adult disease.

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