Department of Biology, Alexandru Ioan Cuza University, Bd. Carol I, nr. 11, Iasi 700506, Romania.
J Physiol Biochem. 2012 Mar;68(1):59-69. doi: 10.1007/s13105-011-0119-x. Epub 2011 Oct 18.
One of the most widely used animal models of Parkinson's disease (PD) involves injecting 6-hydroxydopamine (6-OHDA) directly into the substantia nigra (SN). Some recent reports speculated that dopaminergic drugs may exert brain antioxidant activity, which could explain some of their protective actions. In this way, the aim of the present study was to examine the effects of low-dose pergolide on memory deficits and brain oxidative stress in a 6-OHDA-induced rat model of PD. Right-unilateral lesions of the SN were produced with 6-OHDA. Two weeks after neurosurgery, pergolide (0.3 mg/kg/day) was injected intraperitoneally in the 6-OHDA + pergolide and sham-operated + pergolide groups, while sham-operated and 6-OHDA alone groups received saline. Radial-8-arm maze and Y-maze were used for memory assessment. We also determined some enzymatic antioxidant defenses like superoxide dismutase or glutathione peroxidase and a lipid peroxidation marker [malondialdehyde (MDA)], from the temporal lobe. A reduced number of working/reference memory errors was observed in 6-OHDA + pergolide group, compared to sham-operated rats. Additionally, post hoc analysis showed significant differences between 6-OHDA and 6-OHDA + pergolide groups in both Y-maze and radial-arm-maze tasks. We also noted a significant decrease of MDA level in the 6-OHDA + pergolide group, compared to sham-operated rats. Significant correlations were also found between behavioral parameters and MDA levels. Our data suggest that pergolide facilitates spatial memory and improves brain oxidative balance, after a 6-OHDA-induced model of PD. This could be useful for further investigations and clinical applications of pergolide.
帕金森病（PD）的最广泛使用的动物模型之一涉及将 6-羟多巴胺（6-OHDA）直接注射到黑质（SN）中。一些最近的报告推测，多巴胺能药物可能发挥脑抗氧化活性，这可以解释其一些保护作用。因此，本研究的目的是研究低剂量培高利特对 6-OHDA 诱导的 PD 大鼠模型中记忆缺陷和大脑氧化应激的影响。用 6-OHDA 对 SN 进行右侧单侧损伤。神经手术后两周，6-OHDA +培高利特和假手术+培高利特组腹腔内注射培高利特（0.3mg/kg/天），而假手术和 6-OHDA 单独组给予生理盐水。放射状 8 臂迷宫和 Y 迷宫用于记忆评估。我们还从颞叶测定了一些酶抗氧化防御，如超氧化物歧化酶或谷胱甘肽过氧化物酶和脂质过氧化标志物[丙二醛（MDA）]。与假手术大鼠相比，6-OHDA +培高利特组的工作/参考记忆错误数量减少。此外，事后分析显示，在 Y 迷宫和放射状臂迷宫任务中，6-OHDA 和 6-OHDA +培高利特组之间存在显着差异。与假手术大鼠相比，6-OHDA +培高利特组的 MDA 水平也显着降低。还发现行为参数与 MDA 水平之间存在显着相关性。我们的数据表明，培高利特可促进空间记忆并改善大脑氧化平衡，在 6-OHDA 诱导的 PD 模型之后。这对于进一步研究和培高利特的临床应用可能是有用的。
