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

作者：Pandey Mritunjay; Borah Anupom; Varghese Merina; Barman Pijus Kanti; Mohanakumar Kochupurackal P^*; Usha Rajamma

来源：Neurochemistry International, 2009, 55(6): 431-437.

DOI：10.1016/j.neuint.2009.04.013

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

We tested the hypothesis that dopamine contributes significantly to the hydroxyl radical ((OH)-O-center dot)-induced striatal neurotoxicity caused by 3-nitropropionic acid (3-NP) in a rat model of Huntington's disease. Dopamine (10-100 mu M) or 3-NP (10-1000 mu M) individually caused a significant increase in the generation of hydroxyl radical ((OH)-O-center dot) in the mitochondria, which was synergistically enhanced when the lowest dose of the neurotoxin (10 mu M) and dopamine (100 mu M) were present together. Similarly, systemic administration Of L-DOPA (100-250 mg/kg) and a low dose of 3-NP (10 mg/kg) potentiated (OH)-O-center dot 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 (OH)-O-center dot 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 alpha-methyl-p-tyrosine prior to 3-NP administration. These results strongly implicate a major contributory role of striatal dopamine in increased generation of (OH)-O-center dot, which leads to striatal neurodegeneration and accompanied behavioral changes, in 3-NP model of Huntington's disease.

• 出版日期2009-11