Michael,
Much of the research on environmental toxins and PD has been funded by
National Institute of Environmental Health Sciences (NIEHS) . There is a
lot of information on their web site :
www.niehs.nih.gov

A report on one NIEHS  sponsored Parkinson's research program is shown
below.  We heard Dr. Cory-Slechta speak on this topic at the recent PD
symposium in Rochester, NY. She is a dedicated researcher and advocate. I
don't think the funding for NIEHS Parkinson' s research in FY 2002 has
been appropriated yet.
Linda Herman

Combination of Two Widely Used Pesticides Linked to Parkinson's Disease
Press Reslease
University of Rochester Medical Center

Scientists have shown that the combination of two widely used
agricultural
pesticides-but neither one alone-creates in mice the exact pattern of
brain
damage that doctors see in patients with Parkinson's disease. The
research
offers the most compelling evidence yet that everyday environmental
factors may
play a role in the development of the disease.

The latest findings of the team led by Deborah Cory-Slechta, Ph.D.,
professor of
environmental medicine and dean for research at the University of
Rochester
School of Medicine and Dentistry, appear in the Dec. 15 issue of the
Journal of
Neuroscience. The scientists caution that more studies are necessary to
explain
the link, since it's probable that many factors contribute to a complex
disease
like Parkinson's, and they say it's unlikely that the pesticides on their
own
actually cause the disease.

Cory-Slechta's team studied the effects of a mixture of two very common
agrichemicals, the herbicide paraquat and the fungicide maneb. Each is
used by
farmers on millions of acres in the United States alone: Maneb is applied
widely
on such crops as potatoes, tomatoes, lettuce and corn, and paraquat is
used on
corn, soybeans, cotton, fruit, and a variety of other products. In the
experiment, mice exposed to either one had little or no brain damage, but
mice
exposed to both share a significant trait with people in the very early
stages
of the disease: Though they appear healthy, key brain cells known as
dopamine
neurons are dying. The mice exposed to the mixture carried nearly all of
the
molecular hallmarks of Parkinson's disease as seen in humans.

"The environmental reality is that several of these chemicals are used on
the
same crops and in the same geographical locations. You've got to get rid
of the
weeds. Then the insects. Then funguses. These are different chemicals
that do
different things, but they're often applied in the same fields," says
Cory-Slechta, who was joined in the research by graduate student Mona
Thiruchelvam and faculty members Eric Richfield, Raymond Baggs, and A.
William
Tank.

The study is one of the first to examine the effects of such chemicals in

tandem. Cory-Slechta notes that current regulations and determinations of
safety
levels are usually based on the effects of single chemicals. "In the real
world,
we're exposed to mixtures of chemicals every day. There are thousands
upon
thousands of combinations; I think what we have found is the tip of the
iceberg," she says. "There are a dozen different fungicides related to
maneb
alone. I don't think we just happened to pick the right chemicals to see
such an
effect."

Maneb, paraquat, and many other pesticides are used in the same
agriculture-rich
areas of the country, including the Midwest, California, Florida and the
Northeast. The map of their use mirrors areas of the country where people
are
more likely to die of Parkinson's disease.
Several epidemiological studies have hinted at a role for pesticides in
the
development of the disease. Studies have found that farmers, people who
live in
rural areas, and people who drink well water are more likely to have the
disease
than people who don't. In addition, just last month, scientists at Emory
University presented evidence that rats given a steady dose of the
natural
pesticide rotenone, used on home-grown fruits and vegetables, develop
Parkinson's­like symptoms. Cory-Slechta's study, which used much lower
levels of
chemicals than the Emory research, is the first to link a combination of
more
widely used pesticides to the disease.

"No one has looked at the effects of studying together some of these
compounds
that, taken by themselves, have little effect," says Cory-Slechta. "This
has
enormous implications."

Currently scientists have little understanding of what causes
Parkinson's, where
a tiny group of dopamine-producing neurons deep within an area of the
brain
known as the substantia nigra die. This cell death leads to a shortage of
the
neurotransmitter dopamine and to the tremors, rigidity, and slow movement
that
mark the disease as it progresses slowly over a period of years or
decades.
Parkinson's affects about 1 million people in North America.

There is a growing consensus among scientists that both genetic
predisposition
and environmental agents may play a role in the disease. Doctors see a
similar
effect in heart disease, where a patient might have both a family history
and a
sedentary lifestyle, or in cancer, where certain genes may make one prone
to
develop colon cancer and a poor diet makes the disease even more likely.
Cory-Slechta thinks it's unlikely that exposures to such chemicals
actually
cause Parkinson's on their own, but they may contribute to the
development of
the disease. "This is the first time that truly environmental risk
factors for
Parkinson's disease have been identified," she says.

Cory-Slechta heads a research center funded by the National Institute of
Environmental Health Sciences where researchers study the effects of
environmental agents like cigarette smoke, air pollution, and metals like

mercury and lead on human health. She believes scientists must do more
research
on the effects of exposure to multiple chemicals. "It's a huge problem to
start
thinking about a nearly infinite array of mixtures of chemicals, instead
of the
risk that a single chemical might pose," she says.

She also says more work must be done to see how much of these chemicals
people
are actually exposed to. Usually it's not clear exactly how much of a
pesticide
remains on crops by the time they reach the dinner table. Maneb
frequently shows
up as a slight residue, she says, while paraquat usually shows up just in
trace
amounts; exposures can also occur via other routes. Oftentimes the two
are used
at different stages of the growing cycle. "The real issue is what happens
when
they hit humans in the food chain. If they're both present, then you are
exposed
to the combination."

In the Journal of Neuroscience paper, and in an earlier paper in Brain
Research,
the scientists showed how mice injected with both maneb and paraquat
differed
from normal mice in many ways. Most obviously, the mice moved around much
less;
immediately after the last of 12 injections over six weeks, the mice ran
around
their cages just one-tenth as much as their normal counterparts. More
importantly, the mice that received both chemicals showed brain damage in

exactly the same way as humans with Parkinson's:

  The amount of a key molecular marker, tyrosine hydroxylase, that is one

  measure of the health of the dopamine system was lower by about 15
percent in
  the mice, in the exact same areas of the brain that are damaged by the
  disease. Other closely related areas of the brain were spared, as in
humans.
  The mice had nearly four times as many "reactive astrocytes,"
structures which
  indicate brain damage, compared to the control mice, in areas affected
by
  Parkinson's disease.
  The mice had about 15 percent fewer dopamine neurons and ultimately
produced
  about 15 percent less dopamine than normal mice.

The team is currently pursuing several new avenues of research, with
funding
from NIEHS. For instance, preliminary findings indicate that the
Parkinson's-like effects on mice may be permanent, and that older mice
may be
more sensitive to the combination than younger mice. The team is also
studying
the effects of exposure to the mixture early in life, and they've shown
that
mice with the same genetic abnormality that causes some people to develop

Parkinson's are specially vulnerable to the mixture.

National Institute of Environmental Health Sciences (NIEHS) Center
Program
Last Updated:06/18/2001 07:28:52
http://www.niehs.nih.gov/centers/2001news/ctrnews5.htm

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