Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, 3414951414, Iran.
Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran.
Neurochem Res. 2018 May;43(5):1086-1095. doi: 10.1007/s11064-018-2522-y. Epub 2018 Apr 3.
Epidemiological studies indicate that a higher plasma level of uric acid (UA) associates with the reduced risk of Parkinson's disease (PD). To confirm the role of UA as a biomarker for PD, we evaluated changes in the serum UA level in the 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonism in rat. For this purpose, 6-OHDA was administered in the medial forebrain bundle by stereotaxic surgery. According to the apomorphine-induced rotational test, the increased intensity of behavioral symptoms as a function of time was associated with the further reduction of UA level. On the other hand, the level of UA increased in the midbrain of the injured hemisphere. The level of reduction in the serum UA level of rats with severe and moderate symptoms was significantly higher than that of rats with mild symptoms. The immunohistofluorescence and biochemical analyses showed that the serum UA level was also correlated with the death of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), reduced level of striatal dopamine, and severity of oxidative stress in the midbrain. The rats with mild symptoms also showed a significant decrease in TH-positive neurons and striatal dopamine level. These findings suggest a positive correlation between the level of reduction in the serum urate level and severity of 6-OHDA-induced Parkinsonism. In addition, our findings indicated that UA had no marked neuroprotective effects, at least at concentrations obtained in this study. On the other hand, UA was introduced as a biomarker for PD, as a significant decline was observed in the serum UA level of rats with mild behavioral symptoms but with significant dopaminergic cell death in the SNc.
流行病学研究表明，较高的血浆尿酸（UA）水平与帕金森病（PD）风险降低相关。为了确认 UA 作为 PD 生物标志物的作用，我们评估了 6-羟多巴胺（6-OHDA）诱导的大鼠半帕金森病中血清 UA 水平的变化。为此，通过立体定向手术将 6-OHDA 注射到中脑束。根据阿扑吗啡诱导的旋转试验，行为症状强度随时间的增加与 UA 水平的进一步降低相关。另一方面，损伤半球的中脑中 UA 水平增加。严重和中度症状大鼠的血清 UA 水平降低幅度明显高于轻度症状大鼠。免疫荧光和生化分析表明，血清 UA 水平也与黑质致密部酪氨酸羟化酶（TH）阳性神经元的死亡、纹状体多巴胺水平降低以及中脑氧化应激的严重程度相关。轻度症状的大鼠也表现出 TH 阳性神经元和纹状体多巴胺水平的显著下降。这些发现表明，血清尿酸水平降低的程度与 6-OHDA 诱导的帕金森病的严重程度呈正相关。此外，我们的研究结果表明，UA 没有明显的神经保护作用，至少在本研究中获得的浓度下没有。另一方面，UA 被引入为 PD 的生物标志物，因为在 SNc 多巴胺能细胞死亡明显但行为症状轻微的大鼠中，血清 UA 水平显著下降。
