Alcaraz-Zubeldia Mireya, Boll-Woehrlen Marie Catherine, Montes-López Sergio, Pérez-Severiano Francisca, Martínez-Lazcano Juan Carlos, Díaz-Ruiz Araceli, Ríos Camilo
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez.
Rev Invest Clin. 2009 Sep-Oct;61(5):405-11.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the presence of motor disturbances, derived from the striatal dopamine depletion. Previously, we reported that CuSO4 pretreatment blocked an oxidative stress marker (lipid peroxidation) and prevented the striatal dopamine depletion induced by the administration of the 1-methyl-4-phenylpiridinium (MPP+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a model of PD.
. To determine if tyrosine hydroxylase (TH), the rate-limiting synthetic enzyme of dopamine, is implicated in the neuroprotective effect of CuSO4 pretreatment, and if this neuroprotective effect is able to prevent the hypokinetic state (measured as spontaneous locomotor activity, SLA) induced by the experimental model of PD.
C57 Black/6J mice received a single dose of CuSO4 (2.5 mg/kg, i.p.) either 16 or 24 h before the administration of MPP+ (18 microg/3 microl, i.c.v.). Twenty four hours later, mice SLA was registered and animals sacrificed. Striatal L-DOPA accumulation derived from the administration of a central dopamine descarboxilase inhibitor was evaluated, a strategy considered as a reliable indirect analysis of tyrosine hydroxylase activity (THA).
Administration of, MPP+ decreased SLA (-52%; p = 0.003) as compared to control group values, whereas those mice pretreated with CuSO4 16 h before MPP+, increased SLA by 47% as compared with control group (p = 0.015). Mice pretreated with CuSO4 24 h before MPP+, also showed a statistically significant increase in SLA (71%; p = 0.02), when compared with control group. As a consequence of MPP+ administration, THA was also reduced as compared to control group values (32%; p < 0.05). Reduction of THA was blocked when mice were pretreated with CuSO4 16 h before MPP+. Moreover, mice receiving the CuSO4 24 h before MPP+ showed a significant increase (38%; p < 0.05) in THA when compared with control group.
Results suggest that preservation of THA participates in the neuroprotective effects derived from the copper supplementation, a phenomenon that avoid the hypokinetic state induced by the MPP+ experimental model of PD.
帕金森病（PD）是一种神经退行性疾病，其特征为存在运动障碍，这是由纹状体多巴胺耗竭引起的。此前，我们报道硫酸铜预处理可阻断氧化应激标志物（脂质过氧化），并预防由1-甲基-4-苯基吡啶鎓（MPP+）诱导的纹状体多巴胺耗竭，MPP+是1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的有毒代谢产物，MPTP是帕金森病的一种模型。
确定多巴胺的限速合成酶酪氨酸羟化酶（TH）是否参与硫酸铜预处理的神经保护作用，以及这种神经保护作用是否能够预防帕金森病实验模型诱导的运动减少状态（以自发运动活动，SLA衡量）。
C57黑/6J小鼠在注射MPP+（18μg/3μl，脑室内注射）前16或24小时接受单剂量硫酸铜（2.5mg/kg，腹腔注射）。24小时后，记录小鼠的SLA并处死动物。评估给予中枢多巴胺脱羧酶抑制剂后纹状体L-多巴的积累，这一策略被认为是对酪氨酸羟化酶活性（THA）的可靠间接分析。
与对照组相比，注射MPP+使SLA降低（-52%；p = 0.003），而在MPP+注射前16小时用硫酸铜预处理的小鼠，其SLA比对照组增加了47%（p = 0.015）。在MPP+注射前24小时用硫酸铜预处理的小鼠，与对照组相比，SLA也有统计学上的显著增加（71%；p = 0.02）。由于注射MPP+，与对照组相比，THA也降低了（32%；p < 0.05）。当小鼠在MPP+注射前16小时用硫酸铜预处理时，THA的降低被阻断。此外，在MPP+注射前24小时接受硫酸铜的小鼠与对照组相比，THA有显著增加（38%；p < 0.05）。
结果表明，THA的保留参与了铜补充产生的神经保护作用，这一现象避免了MPP+帕金森病实验模型诱导的运动减少状态。
