Rotenone

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Epidemiological studies have suggested that environmental factors such as pesticides may increase the risk for PD (105). The demonstration of specific neurochemical and pathological damage to dopaminergic neurons by the application of various pesticides such as rotenone have been consistent with these epidemiological findings. Rotenone is an inhibitor of mitochondrial complex I due to impaired oxidative phosphorylation through inhibition of NADH-ubiquitin reductase. For example, using a chronic rotenone infusion paradigm (2 or 3 mg/kg/day for three weeks) through either jugular vein cannulation or systemic delivery with an osmotic pump, Greenamyre et al. reported degeneration of a subset of nigrostriatal dopaminergic neurons; the formation of cytoplasmic inclusions; and the development of parkinsonian motor behavior, including hunched posture, rigidity, unsteady movement, and paw tremor in the rat (106,107). There are some limitations to the rotenone model that one must be aware of, including long administration period of weeks to months; variability due to dose; low animal survival; variable pathological outcomes and specificity; and species and strain differences (108-114). Despite these potential confounders, this model provides valuable insight into one potential mechanism relevant to the etiology of parkinsonism. Studies examining the different parameters of this and other pesticides in animal models may lead to insights into the mechanisms of neuronal death in PD (115).

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