Changes in the Serum Urate Level Can Predict the Development of Parkinsonism in the 6-Hydroxydopamine Animal Model

  • Mohammad Reza Sarukhani
  • Hashem Haghdoost-Yazdi
  • Gilda Khandan-Chelarci
Original Paper
  • 31 Downloads

Abstract

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.

Keywords

Uric acid 6-OHDA-induced hemiparkinsonism Medial forebrain bundle Apomorphine-induced rotational test TH-positive neurons Striatal dopamine level 

Notes

Acknowledgements

We would like to thank Mrs. Ayda Faraji for her assistance in stereotaxic surgeries and Ms. Zare for her contribution to immunohistofluorescence experiments. This study was supported by a Grant-in-aid for scientific research from the Research Council of Qazvin University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cellular and Molecular Research CenterQazvin University of Medical SciencesQazvinIran
  2. 2.Student Research CommitteeQazvin University of Medical SciencesQazvinIran

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