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Chronic systemic pesticide exposure reproduces features of Parkinson's disease

Nature Neuroscience volume 3, pages 1301–1306 (2000) Cite this article

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Abstract

The cause of Parkinson's disease (PD) is unknown, but epidemiological studies suggest an association with pesticides and other environmental toxins, and biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity. Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and α-synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.

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Figure 1: Rotenone infusion selectively and uniformly affected complex I throughout the brain.
Figure 2: Systemic rotenone infusion resulted in nigrostriatal dopaminergic degeneration.
Figure 3: Degeneration of nerve terminals and cell bodies of nigrostriatal dopaminergic neurons in perfusion-fixed brain sections.
Figure 4: Striatal neurons postsynaptic to the degenerating dopaminergic fibers were unaffected by systemic rotenone infusion.
Figure 5: Cytoplasmic inclusions in nigral neurons of rotenone-infused rats.

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Acknowledgements

We thank P. Piccardo and B. Ghetti for donation of the α-synuclein antibody, which was generated with support from the Indiana Alzheimer's Disease Center (P30AG10133). We also thank M. DeLong and A. Levey for reading this manuscript. This work was supported by NIH grants to JTG (NS38399, NS33779, and AG14648).

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  1. Ranjita Betarbet and Todd B. Sherer: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Neurology, Emory University, 1639 Pierce Drive, Atlanta, WMB 6000, Georgia, 30322, USA

    Ranjita Betarbet, Todd B. Sherer, Gillian MacKenzie, Monica Garcia-Osuna, Alexander V. Panov & J. Timothy Greenamyre

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  1. Ranjita Betarbet
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  2. Todd B. Sherer
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Correspondence to J. Timothy Greenamyre.

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Betarbet, R., Sherer, T., MacKenzie, G. et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3, 1301–1306 (2000). https://doi.org/10.1038/81834

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