Mice with a Partial Deficiency of Manganese Superoxide Dismutase Show Increased Vulnerability to the Mitochondrial Toxins Malonate, 3-Nitropropionic Acid, and MPTP

In the present study we investigated the susceptibility of mice with a partial deficiency of SOD2 to the neurotoxins 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 3-nitropropionic acid, and malonate, which are commonly used animal models of Parkinson's and Huntington's disease

Ole A. Andreassen; Robert J. Ferrante; Alpaslan Dedeoglu; David W. Albers; Peter Klivenyi; Elaine J. Carlson; Charles J. Epstein; M.Flint Beal

2002

Scholarcy highlights

  • There is substantial evidence implicating mitochondrial dysfunction and free radical generation as major mechanisms of neuronal death in neurodegenerative diseases
  • In the present study we investigated the susceptibility of mice with a partial deficiency of SOD2 to the neurotoxins 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 3-nitropropionic acid, and malonate, which are commonly used animal models of Parkinson's and Huntington's disease
  • Compared to littermate wild-type mice, mice with partial SOD2 deficiency showed increased vulnerability to dopamine depletion after systemic MPTP treatment and significantly larger striatal lesions produced by both 3-NP and malonate
  • SOD2+/− mice showed an increased production of “hydroxyl” radicals after malonate injection measured with the salicylate hydroxyl radical trapping method
  • These results provide further evidence that reactive oxygen species play an important role in the neurotoxicity of MPTP, malonate, and 3-NP
  • These findings show that a subclinical deficiency in a free radical scavenging enzyme may act in concert with environmental toxins to produce selective neurodegeneration

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