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.

Applying Epigenetics to Alzheimer’s Disease via the Latent Early–life Associated Regulation (LEARn) Model

“…AD does not have a unique status regarding oxidative damage. Differences in guanine oxidation that correlate with symptoms have been found in Parkinson's disease models [100].…”

Parkinson’s Disease: Biomarkers, Treatment, and Risk Factors

“…Therefore, 8-OHdG could be developed as a potential biomarker for PD (Kikuchi et al, 2002). It has been shown in the rat model that PD stage is directly related to urinary 8-OHdG level, suggesting that it can be used as a severity biomarker for PD (Kikuchi et al, 2011). However, it should be remembered that 8-OHdG is a marker of oxidative DNA damage, but not of progression of PD, so its specificity is limited (Simon et al, 2015).…”

Protective effects of cyclosativene on H2O2-induced injury in cultured rat primary cerebral cortex cells

“…6 The scoring criteria for determining damage levels in cultured neurons (A Class 0 (undamaged); B class 1 (slightly damaged); C class 3 (damaged); D class 4 (highly damaged); E class 5 (very highly damaged); F class 6 (extremely damaged) oxidative damage and oxidative DNA damage played important roles in the pathogenesis of many neurodegenerative diseases like Alzheimer's and Parkinson's (Isobe et al 2010). In addition to Comet test, oxidative DNA damage was also evaluated in cell cultures by measuring the 8-OH-dG level, since, in particular, this marker is most frequently measured as an indicator of oxidative DNA damage in neuronal degeneration models both in vitro and in vivo (Kikuchi et al 2011). We observed significant elevation in 8-OH-dG release from neurons was observed after treatment with H 2 O 2 , in contrast, low-dose of CSV pre-treatments led to significant decreases in 8-OH-dG release (Table 4).…”