Bogdanov M B, Ferrante R J, Kuemmerle S, Klivenyi P, Beal M F
Neurochemistry Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
J Neurochem. 1998 Dec;71(6):2642-4. doi: 10.1046/j.1471-4159.1998.71062642.x.
There is substantial evidence for both metabolic dysfunction and oxidative damage in Huntington's disease (HD). In the present study, we used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of hydroxyl radical production in a transgenic mouse model of HD, as well as in littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was unchanged in the striatum of transgenic HD mice at baseline. Following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP), there were significant increases in 3,4-DHBA generation in both control and transgenic HD mice, and the increases in the transgenic HD mice were significantly greater than those in controls. Furthermore, administration of 3-NP produced significantly larger striatal lesions in transgenic HD mice than in littermate controls. The present results show increased sensitivity to the mitochondrial toxin 3-NP in transgenic HD mice, which suggests metabolic dysfunction in this mouse model of HD.
有大量证据表明亨廷顿舞蹈症（HD）存在代谢功能障碍和氧化损伤。在本研究中，我们利用体内微透析技术，在HD转基因小鼠模型及其同窝对照小鼠中，测量4-羟基苯甲酸向3,4-二羟基苯甲酸（3,4-DHBA）的转化，以此作为羟自由基产生的指标。在基线时，转基因HD小鼠纹状体中4-羟基苯甲酸向3,4-DHBA的转化未发生变化。给予线粒体毒素3-硝基丙酸（3-NP）后，对照小鼠和转基因HD小鼠的3,4-DHBA生成均显著增加，且转基因HD小鼠的增加幅度显著大于对照小鼠。此外，给予3-NP后，转基因HD小鼠纹状体中的损伤明显大于同窝对照小鼠。目前的结果表明，转基因HD小鼠对线粒体毒素3-NP的敏感性增加，这表明该HD小鼠模型存在代谢功能障碍。
