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Striatal dopamine level contributes to hydroxyl radical generation and subsequent neurodegeneration in the striatum in 3-nitropropionic acid-induced Huntington's disease in rats.
Neurochem Int. 2009 Nov; 55(6):431-7.NI

Abstract

We tested the hypothesis that dopamine contributes significantly to the hydroxyl radical (OH)-induced striatal neurotoxicity caused by 3-nitropropionic acid (3-NP) in a rat model of Huntington's disease. Dopamine (10-100 microM) or 3-NP (10-1000 microM) individually caused a significant increase in the generation of hydroxyl radical (OH) in the mitochondria, which was synergistically enhanced when the lowest dose of the neurotoxin (10 microM) and dopamine (100 microM) 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 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 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, which leads to striatal neurodegeneration and accompanied behavioral changes, in 3-NP model of Huntington's disease.

Authors+Show Affiliations

Indian Institute of Chemical Biology (CSIR), Division of Cell Biology & Physiology, Laboratory of Clinical & Experimental Neuroscience, Kolkata 700032, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19410615

Citation

Pandey, Mritunjay, et al. "Striatal Dopamine Level Contributes to Hydroxyl Radical Generation and Subsequent Neurodegeneration in the Striatum in 3-nitropropionic Acid-induced Huntington's Disease in Rats." Neurochemistry International, vol. 55, no. 6, 2009, pp. 431-7.
Pandey M, Borah A, Varghese M, et al. Striatal dopamine level contributes to hydroxyl radical generation and subsequent neurodegeneration in the striatum in 3-nitropropionic acid-induced Huntington's disease in rats. Neurochem Int. 2009;55(6):431-7.
Pandey, M., Borah, A., Varghese, M., Barman, P. K., Mohanakumar, K. P., & Usha, R. (2009). Striatal dopamine level contributes to hydroxyl radical generation and subsequent neurodegeneration in the striatum in 3-nitropropionic acid-induced Huntington's disease in rats. Neurochemistry International, 55(6), 431-7. https://doi.org/10.1016/j.neuint.2009.04.013
Pandey M, et al. Striatal Dopamine Level Contributes to Hydroxyl Radical Generation and Subsequent Neurodegeneration in the Striatum in 3-nitropropionic Acid-induced Huntington's Disease in Rats. Neurochem Int. 2009;55(6):431-7. PubMed PMID: 19410615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Striatal dopamine level contributes to hydroxyl radical generation and subsequent neurodegeneration in the striatum in 3-nitropropionic acid-induced Huntington's disease in rats. AU - Pandey,Mritunjay, AU - Borah,Anupom, AU - Varghese,Merina, AU - Barman,Pijus Kanti, AU - Mohanakumar,Kochupurackal P, AU - Usha,Rajamma, Y1 - 2009/05/04/ PY - 2009/01/13/received PY - 2009/04/20/revised PY - 2009/04/22/accepted PY - 2009/5/5/entrez PY - 2009/5/5/pubmed PY - 2009/10/10/medline SP - 431 EP - 7 JF - Neurochemistry international JO - Neurochem Int VL - 55 IS - 6 N2 - We tested the hypothesis that dopamine contributes significantly to the hydroxyl radical (OH)-induced striatal neurotoxicity caused by 3-nitropropionic acid (3-NP) in a rat model of Huntington's disease. Dopamine (10-100 microM) or 3-NP (10-1000 microM) individually caused a significant increase in the generation of hydroxyl radical (OH) in the mitochondria, which was synergistically enhanced when the lowest dose of the neurotoxin (10 microM) and dopamine (100 microM) 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 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 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, which leads to striatal neurodegeneration and accompanied behavioral changes, in 3-NP model of Huntington's disease. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/19410615/Striatal_dopamine_level_contributes_to_hydroxyl_radical_generation_and_subsequent_neurodegeneration_in_the_striatum_in_3_nitropropionic_acid_induced_Huntington's_disease_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(09)00156-9 DB - PRIME DP - Unbound Medicine ER -