Emory Report
July 10, 2006
Volume 58, Number 34


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July 10 , 2006
Developmental pesticide exposure linked to Parkinson’s

BY Janet Christenbury

A team of Emory researchers has found a connection in laboratory mice between developmental exposure to the pesticide dieldrin during gestation and lactation and an increased risk of developing Parkinson’s disease. The findings are significant because most studies aimed at determining the disease process in Parkinson’s have been focused on events occurring during adulthood, not during developmental stages. The study results are published in The Federation of American Societies for Experimental Biology Journal at www.fasebj.org/papbyrecent.dtl.

The pesticide dieldrin was banned for most uses by the Environmental Protection Agency in 1974, then banned completely in 1987. Dieldrin was most commonly used for insect control in crops and for termite control in home foundations. “While many pesticides have been banned from use today, they still remain in the soil and can take decades to break down, as in the case of dieldrin,” said Gary Miller, senior author, researcher in the Center for Neurodegenerative Disease and associate professor in the Department of Environmental and Occupational Health in the School of Public Health. “Because of dieldrin’s lingering effects, our research focuses on the role of the environment and its effects on Parkinson’s.”

Although most people are diagnosed in mid- to late-life with Parkinson’s, experimental evidence suggests that neurodegeneration begins long before a clinical diagnosis,” said Miller. “Recent research has led to the idea that the etiology of a number of diseases may result from alterations occurring during development. Therefore, we decided to examine whether developmental exposure to dieldrin causes persistent changes to the dopaminergic system and whether these changes can result in increased susceptibility to Parkinson’s.”

Parkinson’s disease is considered a disease of aging, occurring when a group of cells in an area of the brain called the substantia nigra begin to malfunction and die. These cells produce a chemical called dopamine, a neurotransmitter or chemical messenger, that sends information to the parts of the brain that control movement and coordination. When a person has Parkinson’s disease, his or her dopamine-producing cells begin to die, leaving that person incapable of initiating and controlling movements in a normal way.

The researchers administered 0.3 mg/kg, 1 mg/kg, 3 mg/kg of dieldrin or no dieldrin (placebo) every three days to pregnant mice throughout gestation and lactation.

“Through analysis of brain samples, we found the pesticide does not directly kill the dopamine neurons, but instead alters the dopamine neuron homeostasis or equilibrium to cause increased vulnerability to a parkinsonism-inducing toxin,” said Miller. The study also found the enhanced vulnerability affected male rodent offspring more so than female rodent offspring. The finding is consistent with that observed in the human population affected by the disease, in that Parkinson’s affects more men than women.

“We also noted that exposure to dieldrin during critical periods of development may lead to the imprinting of genes that regulate the proper formation and maintenance of function of the dopamine system,” said Jason Richardson, co-author and postdoctoral fellow in the Miller laboratory. “This alteration may induce a silent state of dopamine dysfunction and an increased vulnerability of dopamine neurons later in life.”

“The results from this study provide a potential molecular mechanism responsible for the association between dieldrin exposure and increased risk of Parkinson’s and suggests that greater attention should be focused on the role of early life exposures and the development of the disease,” said Miller.