Fachbereich Veterinärmedizin



    Chronic rotenone treatment induces behavioral effects but no pathological signs of parkinsonism in mice (2007)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Richter, Franziska
    Hamann, Melanie
    Richter, Angelika
    Journal of Neuroscience Research; 85(3) — S. 681–691
    ISSN: 0360-4012
    Pubmed: 17171705
    Institut für Pharmakologie und Toxikologie

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    14195 Berlin
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    Abstract / Zusammenfassung

    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.