Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson's disease.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      NADH Dehydrogenase/*genetics ; Parkinsonian Disorders/*chemically induced ; Rotenone/*toxicity; Animals ; Behavior, Animal ; Dopamine/metabolism ; Male ; Parkinsonian Disorders/genetics ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra/drug effects ; Substantia Nigra/metabolism ; Substantia Nigra/pathology
    • Abstract:
      It is widely recognized that mitochondrial dysfunction, most notably defects in the NADH-quinone oxidoreductase (complex I), is closely related to the etiology of sporadic Parkinson's disease (PD). In fact, rotenone, a complex I inhibitor, has been used for establishing PD models both in vitro and in vivo. A rat model with chronic rotenone exposure seems to reproduce pathophysiological conditions of PD more closely than acute mouse models as manifested by neuronal cell death in the substantia nigra and Lewy body-like cytosolic aggregations. Using the rotenone rat model, we investigated the protective effects of alternative NADH dehydrogenase (Ndi1) which we previously demonstrated to act as a replacement for complex I both in vitro and in vivo. A single, unilateral injection of recombinant adeno-associated virus carrying the NDI1 gene into the vicinity of the substantia nigra resulted in expression of the Ndi1 protein in the entire substantia nigra of that side. It was clear that the introduction of the Ndi1 protein in the substantia nigra rendered resistance to the deleterious effects caused by rotenone exposure as assessed by the levels of tyrosine hydroxylase and dopamine. The presence of the Ndi1 protein also prevented cell death and oxidative damage to DNA in dopaminergic neurons observed in rotenone-treated rats. Unilateral protection also led to uni-directional rotation of the rotenone-exposed rats in the behavioral test. The present study shows, for the first time, the powerful neuroprotective effect offered by the Ndi1 enzyme in a rotenone rat model of PD.
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    • Grant Information:
      R01NS048441 United States NS NINDS NIH HHS; R01 DK053244 United States DK NIDDK NIH HHS; R01 NS048441 United States NS NINDS NIH HHS; U54ES012068 United States ES NIEHS NIH HHS; R01DK053244 United States DK NIDDK NIH HHS; U54 ES012068 United States ES NIEHS NIH HHS
    • Accession Number:
      03L9OT429T (Rotenone)
      EC 1.6.99.3 (NADH Dehydrogenase)
      VTD58H1Z2X (Dopamine)
    • Publication Date:
      Date Created: 20080117 Date Completed: 20080808 Latest Revision: 20181113
    • Publication Date:
      20240104
    • Accession Number:
      PMC2175531
    • Accession Number:
      10.1371/journal.pone.0001433
    • Accession Number:
      18197244