Striatal dopamine level contributes to hydroxyl radical generation and subsequent neurodegeneration in the striatum in 3-nitropropionic acid-induced Huntington's disease in rats

Mritunjay Pandey, Anupom Borah, Merina Varghese, Pijus Kanti Barman, Kochupurackal P. Mohanakumar, Rajamma Usha

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

We tested the hypothesis that dopamine contributes significantly to the hydroxyl radical ({radical dot}OH)-induced striatal neurotoxicity caused by 3-nitropropionic acid (3-NP) in a rat model of Huntington's disease. Dopamine (10-100 μM) or 3-NP (10-1000 μM) individually caused a significant increase in the generation of hydroxyl radical ({radical dot}OH) in the mitochondria, which was synergistically enhanced when the lowest dose of the neurotoxin (10 μM) and dopamine (100 μM) were present together. Similarly, systemic administration of l-DOPA (100-250 mg/kg) and a low dose of 3-NP (10 mg/kg) potentiated {radical dot}OH generation in the striatum, and the rats exhibited significant decrease in stride length, a direct indication of neuropathology. The pathology was also evident in striatal sections subjected to NeuN immunohistochemistry. The significant changes in stride length, the production of striatal {radical dot}OH and neuropathological features due to administration of a toxic dose of 3-NP (20 mg/kg) were significantly attenuated by treating the rats with tyrosine hydroxylase inhibitor α-methyl-p-tyrosine prior to 3-NP administration. These results strongly implicate a major contributory role of striatal dopamine in increased generation of {radical dot}OH, which leads to striatal neurodegeneration and accompanied behavioral changes, in 3-NP model of Huntington's disease.

Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalNeurochemistry International
Volume55
Issue number6
DOIs
StatePublished - Nov 2009

Keywords

  • Dopamine synthesis inhibition
  • Hydroxyl radical generation
  • Mitochondria
  • NeuN
  • Succinate dehydrogenase inhibition
  • Synergistic increase in oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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