Changes in the Serum Urate Level Can Predict the Development of Parkinsonism in the 6-Hydroxydopamine Animal Model
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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.
KeywordsUric acid 6-OHDA-induced hemiparkinsonism Medial forebrain bundle Apomorphine-induced rotational test TH-positive neurons Striatal dopamine level
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.
- 7.Shulman JM, De Jager PL, Feany MB (2011) Parkinson’s disease: genetics and pathogenesis. Annu Rev Pathol 6:193–222. https://doi.org/10.1146/annurev-pathol-011110-130242 CrossRefPubMedGoogle Scholar
- 16.Alonso A, Rodríguez LA, Logroscino G, Hernán MA (2007) Gout and risk of Parkinson disease: a prospective study. Neurology 69(17):1696–1700. https://doi.org/10.1212/01.wnl.0000279518.10072.df CrossRefPubMedGoogle Scholar
- 22.Andreadou E, Nikolaou C, Gournaras F, Rentzos M, Boufidou F, Tsoutsou A, Zournas C, Zissimopoulos V, Vassilopoulos D (2009) Serum uric acid levels in patients with Parkinson’s disease: their relationship to treatment and disease duration. Clin Neurol Neurosurg 111(9):724–728. https://doi.org/10.1016/j.clineuro.2009.06.012 CrossRefPubMedGoogle Scholar
- 23.Bové J, Perier C (2012) Neurotoxin-based models of Parkinson’s disease. Neuroscience 211:51–76. https://doi.org/10.1016/j.neuroscience.2011.10.057 CrossRefPubMedGoogle Scholar
- 25.Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, San DiegoGoogle Scholar
- 27.Sarookhani MR, Haghdoost-Yazdi H, Sarbazi-Golezari A, Babayan-Tazehkand A, Rastgoo N (2017) Involvement of adenosine triphosphate -sensitive potassium channels in the neuroprotective activity of hydrogen sulfide in the 6-hydroxydopamine- induced animal model of Parkinson’s disease. Behav Pharmacol. https://doi.org/10.1097/FBP.0000000000000358 PubMedGoogle Scholar
- 28.Sarukhani M, Haghdoost-Yazdi H, Sarbazi A, Babayan-Tazehkand A, Dargahi T, Rastgoo N (2018) Evaluation of the antiparkinsonism and neuroprotective effects of hydrogen sulfide in acute 6-hydroxydopamine- induced animal model of Parkinson’s disease: behavioral, histological and biochemical studies. Neurol Res (unpublished data)Google Scholar
- 31.Gong L, Zhang QL, Zhang N, Hua WY, Huang YX, Di PW, Huang T, Xu XS, Liu CF, Hu LF, Luo WF (2012) Neuroprotection by urate on 6-OHDA-lesioned rat model of Parkinson’s disease: linking to Akt/GSK3β signaling pathway. J Neurochem 123(5):876–885. https://doi.org/10.1111/jnc.12038 CrossRefPubMedGoogle Scholar