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Blockade of quinolinic acid-induced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease.

Authors
Ryu, JK; Kim, SU; McLarnon, JG
Citation
Experimental neurology, 187(1):150-159, 2004
Journal Title
Experimental neurology
ISSN
0014-48861090-2430
Abstract
In this study, we have examined the mechanisms involved in pyruvate-mediated neuroprotection against quinolinic acid (QA)-induced striatal damage. QA injection into the striatum caused widespread neuronal damage and extensive areas of lesions in core and penumbra. The involvement of oxidative-mediated striatal damage was suggested by increased expressions of peroxynitrite, marked lipid peroxidation, and formation of DNA oxidative damage products. Administration of pyruvate, a glycolysis end product with antioxidant activity, significantly reduced QA-mediated striatal lesions, neuronal degeneration, and oxidative damage, whereas another energy substrate, lactate, was ineffective against oxidative damage and only partially effective in reducing lesions and neuronal degeneration. Treatment with the iNOS inhibitor aminoguanidine attenuated QA-mediated striatal lesions and reduced oxidative damage, indicating that iNOS activation may be involved in the striatal oxidative damage induced by QA. A role for glial cells in mediating oxidative damage was suggested because pyruvate blocked the expression of iNOS and nitrotyrosine in activated microglia and astrocytes in QA-injected striatum. These data suggest that pyruvate reduces oxidative free radical damage in QA-injected striatum and could have clinical utility in the treatment of Huntington's disease (HD).
MeSH terms
AnimalsDisease Models, AnimalDrug Administration RoutesEnzyme Inhibitors/pharmacologyGuanidines/pharmacologyHuntington Disease/chemically induced/*metabolism/pathologyLactic Acid/pharmacologyMaleNeostriatum/drug effects/*metabolism/pathologyNeuroglia/drug effects/*metabolism/pathologyNeuroprotective Agents/*pharmacologyNitric Oxide Synthase/antagonists & inhibitorsNitric Oxide Synthase Type IIOxidative Stress/drug effectsPyruvic Acid/*pharmacologyQuinolinic Acid/*antagonists & inhibitors/toxicityRatsRats, Sprague-DawleyStereotaxic TechniquesTyrosine/*analogs & derivatives/biosynthesis
DOI
10.1016/j.expneurol.2004.01.006
PMID
15081596
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
김, 승업
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