Urinary 8-OHdG elevations in a partial lesion rat model of parkinson's disease correlate with behavioral symptoms and nigrostriatal dopaminergic depletion

Yoichiro Kikuchi, Takao Yasuhara, Takashi Agari, Akihiko Kondo, Satoshi Kuramoto, Masahiro Kameda, Tomohito Kadota, Tanefumi Baba, Naoki Tajiri, Feifei Wang, Judith T. Tayra, Hanbai Liang, Yasuyuki Miyoshi, Cesario V. Borlongan, Isao Date

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Abstract

Increased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8-OHdG in PD patients. There are few basic laboratory data examining 8-OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). The urinary 8-OHdG level was measured in relation to behavioral and pathological deficits arising from 6-OHDA-induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6-OHDA injection. We collected urine samples with subsequent measurement of 8-OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8-OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8-OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8-OHdG level provides a good index of severity of parkinsonism. Urinary 8-OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6-OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8-OHdG level closely approximate onset and disease progression in PD.

Original languageEnglish
Pages (from-to)1390-1398
Number of pages9
JournalJournal of Cellular Physiology
Volume226
Issue number5
DOIs
Publication statusPublished - May 2011

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Kikuchi, Y., Yasuhara, T., Agari, T., Kondo, A., Kuramoto, S., Kameda, M., Kadota, T., Baba, T., Tajiri, N., Wang, F., Tayra, J. T., Liang, H., Miyoshi, Y., Borlongan, C. V., & Date, I. (2011). Urinary 8-OHdG elevations in a partial lesion rat model of parkinson's disease correlate with behavioral symptoms and nigrostriatal dopaminergic depletion. Journal of Cellular Physiology, 226(5), 1390-1398. https://doi.org/10.1002/jcp.22467