November 27, 2000
Study links Parkinson's with common pesticide
By Sarah Goodwin
In the December issue of Nature Neuroscience, neurology Professor Tim Greenamyre and colleagues show that rotenone, a commonly used organic pesticide, can induce the major features of Parkinsons disease in rats.
These results provide not only a new animal model for testing potential
treatments, but they also support the idea that chronic exposure to environmental
pesticides may contribute to the incidence of Parkinsons in humans.
Parkinsons disease is one of the most common neurodegenerative
diseases, affecting about
Another characteristic feature of the disease is that the brains of Parkinsons
patients contain microscopic protein deposits known as Lewy bodies.
Although some cases of Parkinsons can be attributed to genetic risk
factors, the majority of cases are still unexplained; these so-called
sporadic cases have been proposed to result from environmental
Before this study, the most realistic animal model of Parkinsons
was the so-called MPTP model, in which mice or monkeys are treated with
a drug known as 1, 2, 3, 6-tetrahydropyridine (MPTP).
This model originates from the early 1980s, when a number of heroin addicts
developed sudden and irreversible symptoms of Parkinson-ism after injecting
themselves with an illicit drug preparation contaminated by MPTP. The
reason for the toxic effect is that MPTP (or, more strictly, its derivative
MPP+) inhibits one of the enzymes in mitochondria, which are the intracellular
organelles that provide cells with energy.
Rotenone, like many other pesticides, inhibits the same mitochondrial
enzyme as MPP+, so Greenamyre and colleagues hypothesized that chronic
treatment with low levels of rotenone might produce Parkinsonian symptoms
They administered rotenone intravenously over a period of several weeks
and observed gradual degeneration of the dopamine neurons, accompanied
by behavioral features of Parkinsonism and the formation of structures
that closely resemble Lewy bodies. A likely explanation, Greenamyre speculated,
is that rotenone acts by caused the mitochondria to produce free radicals,
reactive chemicals that produce oxidative damage in a variety of contexts
and have been implicated in many human degenerative diseases.
Rotenone is a naturally occurring pesticide and is widely used both as
an insecticide and as a method for killing fish (as part of water management
programs). It is considered relatively benign compared to many other pesticides.
Although the new study does not prove that rotenone causes Parkinsonism
in humans, it is likely to raise new questions about rotenones safety.
More generally, it lends credence to the idea that chronic exposure to
environmental toxins, including pesticides, may contribute to the incidence
of the disease.
The main risk factor for Parkinsons disease is age, and it has
also been claimed, more controversially, that the disease is associated
with living in rural environments. Determining to what extent pesticide
exposure can account for Parkinsonism will require a great deal of further
The present findings, however, are consistent with the idea that chronic exposure to low levels of environmental toxin may cause cumulative damage to the brains dopamine system, eventually leading to the clinical symptoms of the disease.