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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
Author(s) -
Kikuchi Yoichiro,
Yasuhara Takao,
Agari Takashi,
Kondo Akihiko,
Kuramoto Satoshi,
Kameda Masahiro,
Kadota Tomohito,
Baba Tanefumi,
Tajiri Naoki,
Wang Feifei,
Tayra Judith T.,
Liang Hanbai,
Miyoshi Yasuyuki,
Borlongan Cesario V.,
Date Isao
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22467
Subject(s) - dopaminergic , parkinson's disease , tyrosine hydroxylase , oxidative stress , parkinsonism , medicine , endocrinology , urinary system , dopamine , nigrostriatal pathway , pathogenesis , lesion , chemistry , pathology , substantia nigra , disease
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. J. Cell. Physiol. 226: 1390–1398, 2011. © 2010 Wiley‐Liss, Inc.