Neuroprotective effects of pyruvate in the quinolinic acid rat model of Huntington's disease.
The neuroprotective effects of pyruvate, the end metabolite of glycolysis, were studied in an animal model of Huntington's disease (HD). Intrastriatal injection of quinolinic acid (QA) caused widespread damage to rat striatum as determined from cresyl violet staining and immunohistochemical analysis. Intraperitoneal administration of pyruvate at doses of 500-1000 mg/kg significantly reduced striatal lesions induced by QA. A lower pyruvate concentration of 250 mg/kg was not protective; however, quadruple applications at this dosage was effective in reducing lesion volumes. The protective effects of pyruvate were found over a range of times, from application at the time of QA injection to 1 h post-administration; however, no protection was conferred if pyruvate was applied 30 min prior to QA injection or 3 h post-administration. We also found pyruvate protects different types of striatal neurons against QA toxicity including GABAergic projection neurons, cholinergic interneurons and NADPH-diaphorase interneurons. These results suggest that pyruvate may be effective in reducing neuronal damage in HD.
Ryu
Jae K
JK
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, V6T 1Z3, Vancouver, BC, Canada.
Kim
Seung U
SU
McLarnon
James G
JG
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007395:Interneurons / Q000187:drug effects / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019289:Pyruvic Acid / Q000627:therapeutic use*; D017378:Quinolinic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D019289:Pyruvic Acid; D017378:Quinolinic Acid