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Dopaminochrome induces neuroinflammation in the substantia nigra of Sprague Dawley rats
Author(s) -
Breckenridge Julie Marie,
Zahm Daniel S,
Westfall Thomas C,
Macarthur Heather
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1053.8
Subject(s) - substantia nigra , pars compacta , neuromelanin , neuroinflammation , microglia , neurodegeneration , dopamine , chemistry , proinflammatory cytokine , inflammation , cytotoxic t cell , neuroprotection , pharmacology , neuroscience , endocrinology , medicine , biology , biochemistry , in vitro , disease , dopaminergic
Our lab has observed that dopaminochrome (DAC), an oxidized form of dopamine, is cytotoxic to the mesencephalic cell line MN9D and induces an inflammatory response in the microglial cell line BV2. Dopamine is highly susceptible to oxidation and may form DAC when exposed to an oxidizing environment, leading to polymerization of DAC into neuromelanin, of which DAC is a major component. We believe the formation of DAC and its subsequent aggregation to neuromelanin may play a role in the progression of Parkinson's disease due to its proinflammatory and cytotoxic properties. In this study, we examined the effect of DAC in vivo . DAC (10 nmoles) was stereotaxically injected into the substantia nigra pars compacta (SNpc) of Sprague Dawley rats. Five, ten, and twenty days post‐surgery, the brains were harvested and assessed for inflammation and neurodegeneration. Results to date suggest that acute administration of 10 nmoles DAC is sufficient to induce activation of SNpc resident microglia without any apparent neurodegeneration. The profile of the resulting inflammation and the effect of microglial inhibition prior to DAC injection will be further assessed. (Supported in part by NIGMS 008306)