Laboratorio de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Mexico.
Neurosci Res. 2013 Mar;75(3):250-5. doi: 10.1016/j.neures.2012.12.003. Epub 2013 Jan 5.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by decreased dopamine, intracellular inclusions (Lewy bodies) and brain iron deposits. PD has also been related with reduced ferroxidase activity, diminished antioxidant defenses and lipid peroxidation. Striatal injection of 1-methyl-4-phenylpyridinium (MPP(+)) into rodents reproduces the major biochemical characteristics of PD, including oxidative stress. Copper (Cu) plays an important role as prosthetic group of several proteins involved in iron metabolism and antioxidant responses, such as ceruloplasmin (Cp). In the present study, intraperitoneal CuSO4 injection (10μmol/kg) produced an insignificant increase of Cu content in striatum and midbrain (17.5% and 7%, respectively). After 10 and 11h, Cu induced 6- and 4-fold increase Cp mRNA in midbrain and striatum, respectively. Cu-supplement also produced a time-dependent increase ferroxidase activity in striatal tissue, reaching a maximum 16h after Cu treatment in midbrain; while, ferrous iron content diminished 18% in striatum and 8% in midbrain. In regard the PD model, we found that MPP(+) (10μg/8μL, intrastriatal), induced a significant (P<0.05) reduction of striatal ferroxidase activity; this effect was reverted by Cu pre-treatment 16h before MPP(+). Likewise, Cu-supplement prevented lipid fluorescent products formation in striatum, evaluated (P<0.01) 6h after MPP(+). In the long term, apomorphine-evoked circling behavior was evaluated 6 days after MPP(+) injury; Cu pre-treatment significantly reduced (P<0.05) the apomorphine-induced ipsilateral turns in MPP(+)-lesioned rats. These results suggest that Cu-induced expression of Cp could be an interesting scope against the deleterious effects of iron deposits in PD.
帕金森病（PD）是一种神经退行性疾病，其特征是多巴胺减少、细胞内包涵体（路易体）和脑铁沉积。PD 还与铁氧化酶活性降低、抗氧化防御和脂质过氧化有关。向啮齿动物纹状体注射 1-甲基-4-苯基吡啶鎓（MPP(+））可复制 PD 的主要生化特征，包括氧化应激。铜（Cu）作为参与铁代谢和抗氧化反应的几种蛋白质的辅基（如铜蓝蛋白（Cp））发挥着重要作用。在本研究中，腹腔内注射 CuSO4（10μmol/kg）可使纹状体和中脑的 Cu 含量分别增加 17.5%和 7%。10 和 11 小时后，Cu 分别使中脑和纹状体的 Cp mRNA 增加 6 倍和 4 倍。Cu 补充还使纹状体组织中的铁氧化酶活性呈时间依赖性增加，在 Cu 处理后 16 小时达到中脑的最大值；而纹状体铁含量减少 18%，中脑减少 8%。关于 PD 模型，我们发现 MPP(+)(10μg/8μL，纹状体内)可显著降低（P<0.05）纹状体铁氧化酶活性；这种作用可通过 MPP(+)前 16 小时的 Cu 预处理逆转。同样，Cu 补充可防止纹状体脂质荧光产物的形成，6 小时后评估（P<0.01）。在长期方面，6 天后评估 MPP(+)损伤后阿朴吗啡诱发的旋转行为；Cu 预处理可显著减少（P<0.05）MPP(+)损伤大鼠中阿朴吗啡诱导的同侧旋转。这些结果表明，Cp 的 Cu 诱导表达可能是对抗 PD 中铁沉积有害影响的一个有趣领域。
