Area of Research Emphasis:
Neurotoxicology & Neurodegenerative Disease (NTND)
NTND Overview: There is a continuous concern about the potential effects of neurotoxic chemicals, due in part to the lack of information on the overall magnitude of the problem of environmental neurotoxicity. Indeed, the number of people with neurotoxic disorders and the extent of neurologic disease and dysfunction that result from exposure to toxic chemicals in the environment are not known. Until a few years ago, only a few of the several thousand chemicals in commercial use had been tested for neurotoxicity, though the recent implementation of new guidelines for neurotoxicity and developmental neurotoxicity will, hopefully, help reduce these data gaps. Exposure to neurotoxic substances either in the workplace or through consumption of contaminated food has led to several outbreaks of neurotoxicity. Classical examples are the pesticides leptophos and kepone, triorthotolylphosphate, methylmercury and domoic acid. Occupational and/or environmental exposure to several chemicals such as solvents (e.g., toluene, styrene), metals (e.g., lead, manganese) and pesticides (e.g., organophosphates) are also associated with neurotoxic effects involving the central and/or peripheral nervous systems. Investigators in the neurotoxicology ARE are working in one or more of the following sub-areas: developmental neurotoxicity, role of neurotoxicants in neurodegenerative diseases, role of genetic polymorphisms in determining susceptibility to neurotoxicants, and cellular, biochemical and molecular mechanisms of neurotoxicity.
A major factor that appears to increase the sensitivity to neurotoxic effects is age (thus, there is a strong and natural collaborative link between many faculty in the SSP and NTND AREs). Recently, the potential impact of exposure of infants and children to pesticides is receiving much attention, and may result in a change in the safety factors for these compounds. Investigators in the NTND ARE are actively pursuing various projects in the area of developmental neurotoxicity, in close collaboration with SSP ARE investigators. The elderly also appear to be more susceptible to certain neurotoxic substances, as the decline in structure and function of the nervous system limits its ability to respond to, or to compensate for, toxicant effects. Decreased liver and kidney function may also increase susceptibility to toxic substances. Several epidemiological studies have shown that exposure to certain chemicals may represent a risk factor for the development of Parkinson’s disease, Alzheimer’s disease, or amyotrophic lateral sclerosis. Together with age, genetic predisposition appears to be a risk factor for both neurotoxicity and neurodegenerative diseases. Genetically determined differences in enzymes metabolizing exogenous and/or endogenous substances such as paraoxonase and monoamine oxidase B have been associated with increased neurotoxicity of organophosphorous compounds and increased risk for Parkinson’s disease, respectively. This area of research is also being pursued by several investigators in the NTND ARE. An understanding of the mechanisms of neurotoxicity will lead to the development of new biomarkers of effects and of new therapeutic approaches, will improve our understanding of genetic predisposition, and will ultimately refine the process of risk assessment. Much of the research of the NTND investigators is focused on the understanding of mechanisms of neurotoxicity and neurodegeneration.
NTND Connections: There are eleven researchers affiliated with the CEEH that work in this area of research emphasis (8 Core EHS Investigators and 3 CTS Investigators). Clement Furlong and Lucio Costa have done a great deal of research on the effects of genetic variation of the PON1 gene, a gene that helps determine how the body handles exposure to organophosphates, a class of neurotoxic pesticides. Their research shows that individuals with low levels of PON1 activity are more susceptible to harm from these chemicals. Furlong and Costa have also studied how environmental factors like diet, smoking, and alcohol consumption can influence PON1 activity. Lucio Costa, Zhengui Xia and Harvey Checkoway are working to understand the gene-environment interactions that contribute to neurogenerative diseases like Parkinson’s disease.
Click HERE for a list of all investigators affiliated with the Neurotoxicology and Neurodegenerative Disease ARE.
ARE Director:
Dr. Lucio Costa, UW Dept. of Environmental and Occupational Health Sciences
lgcosta@u.washington.edu
206-543-2831