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Study of Permethrin Yields Clues to Onset of Parkinson's Disease
(from March 31, 2003)

A grant from the U.S. Army has led Virginia Tech researchers to discover that exposure to some insecticides may cause a cascade of chemical events in the brain that could lead to Parkinson's Disease. Jeffrey R. Bloomquist, a neurotoxicologist and associate professor in the university's Department of Entomology, described his findings at the annual meeting of the American Chemical Society in New Orleans this week.

The researchers have documented low-dose effects of permethrin, doses below one-one thousandth of a lethal dose for a mouse, with effects on those brain pathways involved in Parkinson's Disease. The effects are consistent with a pre-parkinsonsian condition, but not yet full-blown parkinsonism.

"We found low-level exposures set in motion a process with an early onset that develops slowly and is persistent," Dr. Bloomquist said. "More surprising is that high-level exposures resulted in few immediate effects that we could observe, but in the longer term there was a delayed effect."

The Virginia Tech researchers studied the levels of dopamine, dopamine transporter protein expression, and the levels of a synaptic protein (alpha-synuclein) in mice exposed to various doses of the insecticide permethrin. The increase in dopamine uptake indicated the mouse's system was reacting to a neurochemical insult caused by the presence of the insecticide. The slow response to high levels of exposure to pesticides is caused, Bloomquist thinks, by the system being overloaded and only after a period of a few weeks is it capable of responding to the insult in the same way as low doses.

In some individuals, dopamine-producing neurons may be challenged by genetic factors or by previous exposure to other neurotoxins. For individuals with a genetic predisposition, exposure to permethrin may trigger chemical events in the brain that result in an increased risk for damage to the area of the brain that is selectively damaged in Parkinson's disease.

The loss of motor skills, resulting in symptoms such as muscle rigidity, shuffling gait, and a rhythmic tremor, has been linked to the loss of dopamine production in the brain. That loss of dopamine is the major neurochemical expression of Parkinson's Disease.

The researchers also found permethrin exposure resulted in an overproduction of the protein alpha-synuclein at low doses. The accumulation of the protein is a major component of the formation of the Lewy bodies, fibrous tangles observed in the brains of patients with Parkinson's Disease.

The studies so far have concentrated on two-week exposures in mice. Dr. Bloomquist hopes to continue the work, looking at longer-term exposure. He is also studying the effects of another widely used pesticide, chlorpyrifos.

Dr. Bloomquist and his co-investigator, Dr. Bradley Klein, are supported by a five year, $584,558 grant from the United States Army Medical Research and Materiel Command. One purpose of the Neurotoxin Exposure Treatment Research Program, under which the project was funded, is to determine if military operational and deployment exposures increase risks for neurodegenerative disease and, if so, determine means of protecting troops.

"Permethrin is used worldwide in agriculture and urban settings," Dr. Bloomquist said. "Widespread human exposure to this compound occurs, so its effects are not limited to soldiers."