Chronic rotenone treatment induces behavioral effects but no pathological signs of parkinsonism in mice.
It has been hypothesized that exposures to neurotoxic pesticides together with aging and genetic factors increase the risk for developing Parkinson's disease (PD) which is characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway. Chronic treatment with the pesticide rotenone has been reported to induce parkinsonism in rats. Although transgenic mice (but not transgenic rats) are available to investigate the importance of environmental factors in genetically predisposed animals, the effects of chronic rotenone exposure have so far not been examined in intact mice. Therefore, we investigated the effects of chronic exposure to rotenone (2.5 or 4.0-5.0 mg/kg s.c. for 30-45 days) in mice aged 2.5, 5, or 12 months. During the treatment period, the effects on vitality and motor behavior were investigated. Furthermore, the toxicity of rotenone on dopaminergic nigrostriatal neurons and peripheral tissues was examined. In comparison with control mice, rotenone-treated mice had a decreased spontaneous motor activity, but the density of nigral dopaminergic neurons failed to show any significant changes, except for a tendency to decrease in old mice treated with 4 mg/kg. At the tested doses, rotenone caused a moderate hepatic fatty degeneration. The data indicate that rotenone is not able to cause the neuropathological characteristics of PD in mice under these testing paradigms, which were similar to those of the rotenone rat model. Further studies will have to clarify whether genetic mouse models of PD might be more sensitive to the neurotoxic effects of rotenone.
Richter
Franziska
F
Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Hamann
Melanie
M
Richter
Angelika
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D005500:Follow-Up Studies; D005684:Gait / Q000187:drug effects; D007794:Lameness, Animal / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D012402:Rotenone / Q000633:toxicity*; D013534:Survival; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase