Chronic exposure to substances like the pesticide rotenone may contribute to
the development of Parkinson’s disease, say neurologists from the United
States.
Dr Ranjita Betarbet and colleagues (department of neurology, Emory university,
Atlanta, Georgia) gave rats continuous intravenous infusions of rotenone for
up to five weeks.
The rats developed symptoms characteristic of Parkinson’s disease (PD),
such as unsteady movement, rigidity and paw shake. They also developed lesions
in the brain that resembled Lewy bodies, which are thought to be involved in
triggering the death of dopaminergic neurones.
The results lend weight to the theory that environmental toxins ingested through
diet or drinking water might contribute to the pathogenesis of PD, the authors
say.
Dr Betarbet and colleagues say that rotenone is derived from plant roots and
is used both as an insecticide in vegetable gardens and to kill fish. It is
known to be a poison that inhibits mitochondrial respiration at complex I of
the electron transport chain. Post mortem studies have shown that mitochondrial
impairment and oxidative damage are “strongly implicated” in the pathogenesis
of PD.
The severity of symptoms exhibited by the rats depended on the extent of the
Lewy body-like lesions, and symptoms persisted even after the infusions of rotenone
had been stopped (Nature Neuroscience 2000;3: 1301).
Commenting on the findings, Drs Benoit Giasson and Virginia Lee (centre for
neurodegenerative disease research, University of Pennsylvania) say that the
results are likely to raise questions about the safety of rotenone, although
its contribution to the incidence of PD remains to be determined. “Although
genetic factors certainly contribute to vulnerability, the most important risk
factor for PD is age, consistent with the idea that chronic exposure to low
levels of noxious substances over time may drive a molecular chain of events
that eventually leads to PD,” they say (Nature Neuroscience 2000;3:1227).