Ryu Jae K, Kim Seung U, McLarnon James G
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, V6T 1Z3, Vancouver, BC, Canada.
Exp Neurol. 2003 Oct;183(2):700-4. doi: 10.1016/s0014-4886(03)00214-0.
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.
在亨廷顿舞蹈病（HD）动物模型中，研究了糖酵解的终末代谢产物丙酮酸的神经保护作用。通过甲酚紫染色和免疫组化分析确定，纹状体内注射喹啉酸（QA）会对大鼠纹状体造成广泛损伤。腹腔注射剂量为500 - 1000 mg/kg的丙酮酸可显著减少QA诱导的纹状体损伤。较低浓度250 mg/kg的丙酮酸没有保护作用；然而，该剂量四倍给药可有效减少损伤体积。丙酮酸的保护作用在从QA注射时给药到给药后1小时的一系列时间范围内均有发现；然而，如果在QA注射前30分钟或给药后3小时应用丙酮酸，则没有保护作用。我们还发现丙酮酸可保护不同类型的纹状体神经元免受QA毒性，包括γ-氨基丁酸能投射神经元、胆碱能中间神经元和还原型辅酶II -黄递酶中间神经元。这些结果表明，丙酮酸可能对减少HD中的神经元损伤有效。
