Evidence for Oxidative DNA Damage in the Hippocampus of Elderly Patients With Chronic Schizophrenia

Nishioka, Naoya; Arnold, Steven E.

doi:10.1097/00019442-200403000-00008

Cited by 98 publications

(40 citation statements)

References 60 publications

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“…Increased urinary 8-OH-dG levels have also been observed in children with brain damage [13]. An immunohistochemical approach showed ten times higher brain level of 8-OH-dG in schizophrenia [14]. A trend towards increased urinary 8-OH-dG levels has been reported in children with autism [15] suggesting the possible modification of DNA in the autistic brain explored in this study.…”

Section: Introductionsupporting

confidence: 67%

“…Human cerebellar 8-OH-dG levels have not been so far quantified. However, a tenfold increase in this marker of oxidative DNA damage has been observed in the hippocampus of older schizophrenic cases [14]. Overall, there was a 63.4% increase in the level of 8-OH-dG in autistic cerebella with three out of five autistic values being higher than the mean control level.…”

Section: Discussionmentioning

confidence: 91%

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Increase in Cerebellar Neurotrophin-3 and Oxidative Stress Markers in Autism

2009

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Autism is a neurodevelopmental disorder characterized by social and language deficits, ritualistic-repetitive behaviors and disturbance in motor functions. Data of imaging, head circumference studies, and Purkinje cell analysis suggest impaired brain growth and development. Both genetic predisposition and environmental triggers have been implicated in the etiology of autism, but the underlying cause remains unknown. Recently, we have reported an increase in 3-nitrotyrosine (3-NT), a marker of oxidative stress damage to proteins in autistic cerebella. In the present study, we further explored oxidative damage in the autistic cerebellum by measuring 8-hydroxydeoxyguanosine (8-OH-dG), a marker of DNA modification, in a subset of cases analyzed for 3-NT. We also explored the hypothesis that oxidative damage in autism is associated with altered expression of brain neurotrophins critical for normal brain growth and differentiation. The content of 8-OH-dG in cerebellar DNA isolated by the proteinase K method was measured using an enzyme-linked immunosorbent assay (ELISA); neurotrophin-3 (NT-3) levels in cerebellar homogenates were measured using NT-3 ELISA. Cerebellar 8-OH-dG showed trend towards higher levels with the increase of 63.4% observed in autism. Analysis of cerebellar NT-3 showed a significant (p = 0.034) increase (40.3%) in autism. Furthermore, there was a significant positive correlation between cerebellar NT-3 and 3-NT (r = 0.83; p = 0.0408). These data provide the first quantitative measure of brain NT-3 and show its increase in the autistic brain. Altered levels of brain NT-3 are likely to contribute to autistic pathology not only by affecting brain axonal targeting and synapse formation but also by further exacerbating oxidative stress and possibly contributing to Purkinje cell abnormalities.

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Section: Introductionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 91%

Increase in Cerebellar Neurotrophin-3 and Oxidative Stress Markers in Autism

2009

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“…This type of oxidative DNA damage has been reported as being associated with a poor prognosis [36]. A study conducted in older patients with schizophrenia and a poor clinical course showed a 10-fold increase in 8-OHdG levels in the hippocampus [37]. Similar 8-OHdG levels in patients and healthy subjects may be due to a lack of oxidative DNA damage in early disease periods in our patients with EOS, and that DNA damage may be associated with a chronic disease course.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and DNA Damage in Untreated First-Episode Psychosis in Adolescents

Şimşek

Gençoğlan

Yüksel³

et al. 2016

Neuropsychobiology

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Objective: Oxidative stress has been reported to play a role in the psychopathology of schizophrenia, though only a few studies have investigated the relationship between early-onset schizophrenia and oxidative stress. The aim of the present study is to evaluate the level of oxidative stress and the presence of DNA damage in first-episode psychosis (FEP) in adolescents. Methods: This study was conducted in the Department of Child Psychiatry of the Dicle University Hospital. It included 20 adolescent patients (age 11-17 years) with psychosis (acute psychosis, schizophreniform disorder, or schizophrenia) according to DSM-IV criteria who had received no previous psychiatric therapy (patient group) and 20 age/gender-matched healthy adolescents (control group). Structured psychiatric interviews [Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL) and Positive and Negative Symptom Scale (PANSS)] were conducted on the patients, and the Clinical Global Impressions (CGI) scale was used to evaluate the severity of disease. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were determined using the ELISA method and commercial ELISA kits. Results: The mean age was 14.5 ± 1.6 years in the FEP group (male-to-female ratio: 8/12) and 14.4 ± 1.5 years in the control group (male-to-female ratio: 8/12). There were no differences between the patient and control groups in terms of SOD, GPx, or 8-OHdG values (p > 0.05). Conclusions: This study on DNA damage and oxidative stress in FEP in adolescents had a small sample size, and our data suggest that oxidative stress is associated with a chronic disease course rather than being an early sign of early-onset schizophrenia.

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“…We dealt with types 3 and 4 as NASH, as described previously by Matteoni et al [3]. Immunoreactivity of 8-hydroxy-2V -deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, in the liver was examined as described previously [20]. Briefly, paraffin sections were incubated with 5 lg/mL of mouse monoclonal anti-8-OHdG (Japan Institute for the Control of Aging, Fukuroi, Japan) overnight followed by incubation with alkaline phosphatase-labeled horse antimouse IgG (Vector, Burlingame, CA) and visualization by diaminobenzidine.…”

Section: Histologic Studiesmentioning

confidence: 99%