BLACKSBURG, Va., March 24, 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, will describe his findings
as part of the International Award for Research in Agrochemicals, a
symposium honoring Robert M. Hollingworth, at the annual meeting of
the American Chemical Society in New Orleans this week.


"We found low-level exposures set in motion a process with an early
onset that develops slowly and is persistent," 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.


"Our studies 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," he said.
"We have found effects consistent with a pre-parkinsonsian condition,
but not yet full-blown parkinsonism."


Bloomquist 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.
Bloomquist hopes to continue the work, looking at longer-term
exposure. He is also studying the effects of another widely used
pesticide, chlorpyrifos.


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,"
Bloomquist said. "Widespread human exposure to this compound occurs,
so its effects are not limited to soldiers."


The talk, "Low-dose effects of insecticides to dopaminergic pathways
involved in parkinsonism" (AGRO 31) will be presented at 2 p.m.
Monday, March 24, in the Hampton Inn Convention Center Fulton room.