Blockade of quinolinic acid-induced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease
Blockade of quinolinic acid-induced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease
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DOI：
10.1016/j.expneurol.2004.01.006
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
McLarnon, JG
中科院分区：
文献类型：
--
作者：
Ryu, JK;Kim, SU;McLarnon, JG
在这项研究中，我们已经研究了涉及的机制，在对喹啉酸（QA）诱导的纹状体损伤的阿托伐酯介导的神经保护。QA注射到纹状体引起广泛的神经元损伤和广泛的区域病变的核心和半影区。氧化介导的纹状体损伤的参与，建议增加过氧亚硝酸盐的表达，显着的脂质过氧化反应，和DNA氧化损伤产物的形成。丙酮酸盐，一种具有抗氧化活性的糖酵解终产物，可显著降低QA介导的纹状体病变、神经元变性和氧化损伤，而另一种能量底物乳酸盐对氧化损伤无效，仅部分有效减少病变和神经元变性。用NOS抑制剂氨基胍处理可减弱QA介导的纹状体损伤并减少氧化损伤，表明NOS激活可能参与QA诱导的纹状体氧化损伤。神经胶质细胞介导的氧化损伤的作用，因为丙酮酸阻断了激活的小胶质细胞和星形胶质细胞在QA注射纹状体的NOS和硝基酪氨酸的表达。这些数据表明，丙酮酸减少QA注射纹状体的氧化自由基损伤，并可能在治疗亨廷顿病（HD）的临床效用。(C)2004年爱思唯尔公司All rights reserved.
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 NOS inhibitor aminoguanidine attenuated QA-mediated striatal lesions and reduced oxidative damage, indicating that NOS 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 NOS 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). (C) 2004 Elsevier Inc. All rights reserved.