Martínez-Lazcano Juan Carlos, Montes Sergio, Sánchez-Mendoza María Alicia, Rodríguez-Páez Lorena, Pérez-Neri Iván, Boll Marie Catherine, Campos-Arroyo Hortensia Denise, Ríos Camilo, Pérez-Severiano Francisca
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Insurgentes Sur #3877, Col. La Fama, Del. Tlalpan, 14269, D.F., Mexico City, Mexico.
Biol Trace Elem Res. 2014 Dec;162(1-3):211-8. doi: 10.1007/s12011-014-0127-0. Epub 2014 Oct 16.
Quinolinic acid (QUIN) striatal injection in rat reproduces the main neurochemical features of Huntington's disease (HD), including oxidative damage. In this study, we evaluated the effect of a copper (Cu) supplement in drinking water (90 ppm Cu, 28 days) on the QUIN-induced HD model in the rat. Copper exposure caused no signs of liver toxicity; however, it produced significant Cu accumulation in striatum. It is noteworthy that QUIN also caused increased striatal Cu content; when the supplement was administered to animals with QUIN-injury, an even higher metal striatal accumulation was observed. Cu pre-treatment preserved striatal gamma-aminobutyric acid (GABA) content, which was reduced by QUIN intrastriatal injection. Similarly, apomorphine-induced circling behavior was reduced in Cu-pretreated QUIN-damaged rats. Metal supplement in drinking water prevented both lipid peroxidation and reactive oxygen species (ROS) formation caused by QUIN in striatum. In Cu-treated groups, superoxide dismutase-1 (SOD1) activity showed a significant increase, while SOD2 activity was slightly enhanced. Although the pathophysiological role for higher Cu levels in patients with HD and in experimental models of the disease is not fully understood, results in the present study suggest that Cu oral intake stimulates anti-oxidant defenses, an effect that may be a potential factor for reducing the progression of HD.
在大鼠纹状体内注射喹啉酸（QUIN）可重现亨廷顿舞蹈病（HD）的主要神经化学特征，包括氧化损伤。在本研究中，我们评估了饮用水中添加铜（Cu，90 ppm，持续28天）对大鼠QUIN诱导的HD模型的影响。铜暴露未引起肝脏毒性迹象；然而，它导致纹状体内铜显著蓄积。值得注意的是，QUIN也导致纹状体铜含量增加；当给QUIN损伤的动物补充铜时，观察到纹状体内金属蓄积更高。铜预处理可维持纹状体内γ-氨基丁酸（GABA）含量，而纹状体内注射QUIN会使其降低。同样，在铜预处理的QUIN损伤大鼠中，阿扑吗啡诱导的转圈行为减少。饮用水中的金属补充剂可防止QUIN在纹状体中引起的脂质过氧化和活性氧（ROS）形成。在铜处理组中，超氧化物歧化酶-1（SOD1）活性显著增加，而SOD2活性略有增强。尽管HD患者及该疾病实验模型中较高铜水平的病理生理作用尚未完全明确，但本研究结果表明，口服铜可刺激抗氧化防御，这一作用可能是减缓HD进展的一个潜在因素。
