Striatal Dopamine Level Contributes to Hydroxyl Radical Generation and Subsequent Neurodegeneration in the Striatum in 3-nitropropionic Acid-Induced Huntington’s Disease in Rats
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Striatal Dopamine Level Contributes to Hydroxyl Radical Generation and Subsequent Neurodegeneration in the Striatum in 3-nitropropionic Acid-Induced Huntington’s Disease in Rats
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| Creator |
Pandey, Mritunjay
Borah, Anupom Varghese, Merina Barman, Pijush Kanti Mohanakumar, K P Usha, Rajamma |
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| Subject |
Cancer Biology and Inflammatory Disorder Division
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| Description |
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 mM) or 3-NP (10–1000 mM) individually caused a significant increase in the
generation of hydroxyl radical (�OH) in themitochondria, which was synergistically enhanced when the
lowest dose of the neurotoxin (10 mM) and dopamine (100 mM) 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 a-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.
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| Date |
2009
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/970/1/7_NI_2009.pdf
Pandey, Mritunjay and Borah, Anupom and Varghese, Merina and Barman, Pijush Kanti and Mohanakumar, K P and Usha, Rajamma (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). pp. 431-437. |
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| Relation |
http://dx.doi.org/:10.1016/j.neuint.2009.04.013
http://www.eprints.iicb.res.in/970/ |
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