1-Methyl-4-phenylpyridinium ion (MPP⁺)-induced neurotoxicity produces cellular damage resembling that encountered in Parkinson’s disease. The mechanisms of cellular death after MPP⁺ include the participation of oxidative stress in the loss of dopaminergic neurons. Among the mechanisms of defense against oxidative stress, several copper-dependent proteins have been implicated: Cu/Zn-SOD, ceruloplasmin, and metallothionein. Another important mechanism of damage, is MPP + interference with mitochondrial respiration. Both, oxidative stress and inhibition of mitochondrial respiration may trigger apoptosis in the neurons after MPP⁺. The aim of the present study was to characterize the time-course of apoptosis induced by MPP⁺ to determine if copper sulfate pretreatment is able to prevent the activation of caspases and decreased the neuronal apoptosis. MPP⁺ was microinjected into rat striatum using a stereotactic frame. The results showed increased activities of caspases 8, 9 and 3, between 72–120 hours after administration of MPP⁺, both in striatum and midbrain. After this study, we tested the effect of CuSO₄ on MPP⁺ neurotoxicity, showing a diminution of the apoptotic damage induced by MPP⁺, decreased levels of enzymatic activity of caspases: 8 (-34 and -25 %), 9 (-25 and -42 %) and 3 (-40 and -29 %) in striatum and midbrain, respectively. Finally, we performed an immunohistochemical analysis, evidencing a decreased number of apoptotic cells in the groups pretreated with copper sulfate pretreatment compared to the control group. With these findings, it is concluded that pretreatment with copper sulfate may be a good alternative to prevent MPP⁺-induced apoptosis.

1-甲基-4-苯基吡啶鎓离子 (MPP ⁺ ) 诱导的神经毒性产生类似于帕金森病中遇到的细胞损伤。MPP ⁺后细胞死亡的机制包括氧化应激参与多巴胺能神经元的丧失。在抵御氧化应激的机制中，涉及几种铜依赖性蛋白质：Cu/Zn-SOD、铜蓝蛋白和金属硫蛋白。另一个重要的损伤机制是 MPP + 干扰线粒体呼吸。MPP ⁺后，氧化应激和线粒体呼吸抑制都可能引发神经元凋亡。本研究的目的是表征 MPP ⁺诱导的细胞凋亡的时间过程以确定硫酸铜预处理是否能够阻止半胱天冬酶的激活并减少神经元凋亡。使用立体定向框架将MPP ⁺显微注射到大鼠纹状体中。结果显示，在施用 MPP ⁺后 72-120 小时，纹状体和中脑中caspase 8、9 和 3 的活性增加。在这项研究之后，我们测试了 CuSO ₄对 MPP ⁺神经毒性的影响，表明 MPP ⁺诱导的细胞凋亡损伤减少, caspase 的酶活性水平降低：纹状体和中脑分别为 8（-34 和 -25 %）、9（-25 和 -42 %）和 3（-40 和 -29 %）。最后，我们进行了免疫组织化学分析，证明与对照组相比，硫酸铜预处理组的凋亡细胞数量减少。根据这些发现，可以得出结论，用硫酸铜预处理可能是防止 MPP ⁺诱导的细胞凋亡的良好替代方案。