Transgenic ALS mice show increased vulnerability to the mitochondrial toxins MPTP and 3-nitropropionic acid

Ole A. Andreassen, Robert J. Ferrante, P. Klivényi, Autumn M. Klein, Alpaslan Dedeoglu, David S. Albers, Neil W. Kowall, M. Flint Beal

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The pathogenesis of neurodegenerative diseases may involve a genetic predisposition acting in concert with environmental toxins. To test this hypothesis we examined whether transgenic mice with the G93A mutation in Cu,Zn superoxide dismutase show increased vulnerability to either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3-NP). Compared to littermate controls G93A transgenic mice showed a greater loss of striatal dopamine, DOPAC, and HVA at 50, 70, and 120 days of age following administration of MPTP; however, cell loss in the substantia nigra was not greater. The G93A transgenic mice showed significantly increased vulnerability to striatal lesions produced by 3-NP compared with littermate controls at 120 days of age. The finding that G93A mice show increased vulnerability to mitochondrial toxins further implicates mitochondrial dysfunction in the pathogenesis of neuronal death in these mice. The findings support the hypothesis that a genetic defect can increase susceptibility to environmental toxins and that this may play a role in the pathogenesis of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)356-363
Number of pages8
JournalExperimental Neurology
Volume168
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Transgenic Mice
Corpus Striatum
Neurodegenerative Diseases
3,4-Dihydroxyphenylacetic Acid
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Substantia Nigra
Genetic Predisposition to Disease
Dopamine
Mutation
3-nitropropionic acid
4-phenyl-1,2,3,6-tetrahydropyridine
Superoxide Dismutase-1

Keywords

  • 3-Nitropropionic acid
  • Amyotrophic lateral sclerosis
  • Mitochondria
  • MPTP
  • Oxidative damage
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Andreassen, O. A., Ferrante, R. J., Klivényi, P., Klein, A. M., Dedeoglu, A., Albers, D. S., ... Beal, M. F. (2001). Transgenic ALS mice show increased vulnerability to the mitochondrial toxins MPTP and 3-nitropropionic acid. Experimental Neurology, 168(2), 356-363. https://doi.org/10.1006/exnr.2001.7627

Transgenic ALS mice show increased vulnerability to the mitochondrial toxins MPTP and 3-nitropropionic acid. / Andreassen, Ole A.; Ferrante, Robert J.; Klivényi, P.; Klein, Autumn M.; Dedeoglu, Alpaslan; Albers, David S.; Kowall, Neil W.; Beal, M. Flint.

In: Experimental Neurology, Vol. 168, No. 2, 2001, p. 356-363.

Research output: Contribution to journalArticle

Andreassen, OA, Ferrante, RJ, Klivényi, P, Klein, AM, Dedeoglu, A, Albers, DS, Kowall, NW & Beal, MF 2001, 'Transgenic ALS mice show increased vulnerability to the mitochondrial toxins MPTP and 3-nitropropionic acid', Experimental Neurology, vol. 168, no. 2, pp. 356-363. https://doi.org/10.1006/exnr.2001.7627
Andreassen, Ole A. ; Ferrante, Robert J. ; Klivényi, P. ; Klein, Autumn M. ; Dedeoglu, Alpaslan ; Albers, David S. ; Kowall, Neil W. ; Beal, M. Flint. / Transgenic ALS mice show increased vulnerability to the mitochondrial toxins MPTP and 3-nitropropionic acid. In: Experimental Neurology. 2001 ; Vol. 168, No. 2. pp. 356-363.
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