Source: Salk InstitutePrint this pageDate: 2003-03-18
URL: http://www.sciencedaily.com/releases/2003/03/030318072141.htm
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Genetic Link May Tie Together Pesticides, ADHD, Gulf War Syndrome And Other
Disorders
La Jolla, Calif. -- Research at the Salk Institute has identified a gene that
may link certain pesticides and chemical weaponry to a number of neurological
disorders, including the elusive Gulf War syndrome and attention deficit/hyperactivity
disorder (ADHD).
The finding, published in the March 17 online version of Nature Genetics, is
the first to demonstrate a clear genetic link between neurological disorders
and exposure to organophosphate chemicals; the gene is one that scientists had
not studied in previous efforts to find connections between these chemicals
and disease. Organophosphates include household pesticides as well as deadly
nerve gases like sarin.
Dr. Carrolee Barlow, who led the work at the Salk Institute and is now at Merck
and Co., Inc., and her team, headed by Christopher Winrow, found in mice that
organophosphate exposure inhibited the activity of a gene called neuropathy
target esterase, or NTE. This inhibition either killed the mice before birth,
or over time led to a range of behaviors very similar to ADHD. Some of the neurological
problems also echoed many of the symptoms seen in Gulf War syndrome.
"There have been anecdotal links made between rises in ADHD, Parkinson's
disease and other disorders and exposure to pesticides," said Barlow, an
adjunct faculty member at the Salk. "There also has been suspicion of a
link to Gulf War syndrome. But scientists have been focusing on enzymes that
act on acetylcholine neurotransmitters. This study shows that there may indeed
be a genetic connection that explains how organophosphates can cause these reactions;
it's just not what we assumed it would be."
Barlow's group had originally been looking at how environmental factors immediately
affect the nervous system. They found that mice bred to lack the NTE gene died
before birth. But the group also found that mice with only one copy of the NTE
gene, when exposed to experimental organophosphates and examined over a prolonged
period, exhibited behavior similar to ADHD.
The mice with only one NTE copy had a 40 percent decrease in the NTE enzyme
produced by the NTE gene. The mice with normal NTE genes also showed ADHD-like
behavior, though to a lesser degree, when exposed to organophosphates. The gene
is active in parts of the brain controlling movement, including the hippocampus,
the cerebellum and the spinal cord.
"NTE is a large gene," said Barlow. "It's possible that we all
have slightly different forms of the NTE enzyme, which may explain why some
may get ADHD when they're exposed at young ages, and why some may get Gulf War
syndrome at a later age, or why some of us have no symptoms at all. It appears
to be a case of delayed toxicity, inhibiting the function of NTE."
At the Salk, researcher Matthew Hemming in Professor Stephen Heinemann's laboratory
is continuing to work on unlocking the secrets of NTE's activity. The Salk team
is working to detail how losing NTE function results in behavioral and neurological
changes, as well as focusing on what happens when the gene for NTE is turned
off in one part of the brain, but working in other areas.
The Gulf War syndrome is a loosely defined collection of symptoms, ranging from
headache and fever to severe forgetfulness and movement disorders. It was first
noted after Operations Desert Storm and Desert Shield in 1991, when U.S., Canadian
and British military veterans reported more symptoms than soldiers who were
not deployed. Its cause is unknown.
The researchers are supported by a $1.5 million grant from the U.S. Department
of Defense. Barlow's colleagues on the project include Christopher Winrow, Duane
Allen, and, Gary Quistad and John Casida of the University of California, Berkeley.
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an
independent nonprofit organization dedicated to fundamental discoveries in the
life sciences, the improvement of human health and conditions, and the training
of future generations of researchers. The institute was founded in 1960 by Jonas
Salk, M.D., with a gift of land from the City of San Diego and the financial
support of the March of Dimes Birth Defects Foundation.
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This story has been adapted from a news release issued by Salk Institute.
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