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

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.

journal_name

J Cell Physiol

journal_title

Journal of cellular physiology

authors

Kikuchi Y,Yasuhara T,Agari T,Kondo A,Kuramoto S,Kameda M,Kadota T,Baba T,Tajiri N,Wang F,Tayra JT,Liang H,Miyoshi Y,Borlongan CV,Date I

doi

10.1002/jcp.22467

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

1390-8

issue

eissn

0021-9541

issn

1097-4652

journal_volume

226

pub_type

杂志文章

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