Oxidative damage to RNA but not DNA in the hippocampus of patients with major mental illness

Abstract

Background: Oxidative damage in the central nervous system is increasingly recognized as an important pathological process in many diseases. Previously, our laboratory found that oxidative damage to lipids and proteins was increased in postmortem brain tissue from patients with bipolar disorder and schizophrenia. In the current study, we analyzed oxidative damage to nucleic acids in the CA1, CA3 and dentate gyrus regions of postmortem hippocampus tissue from patients with bipolar disorder, schizophrenia and major depression. Methods: We examined oxidative damage to nucleic acids by performing immunohistochemistry with a monoclonal antibody that recognizes both 8-hydroxy-guanosine in RNA and 8-hydroxy-2'-deoxyguanosine in DNA. Results: We found that the amount of oxidative damage to nucleic acids was elevated in the CA1, CA3 and dentate gyrus regions of the hippocampus among patients with bipolar disorder, schizophrenia and major depressive disorder. This damage was predominantly in the cytoplasm, suggesting that the damage was primarily to RNA. Compared with oxidative damage in control samples, the magnitude of damage was high in patients with schizophrenia, modest in patients with bipolar disorder and lower in patients with major depression. Limitations: The interpretation of our results is limited by a number of factors, including the retrospective review of patient history, the relatively small sample size and the inclusion of patients who had substance abuse and were undergoing various drug treatments at the time of death. Conclusion: Our results suggest that oxidative damage to RNA, rather than to DNA, occurs in vulnerable neurons of the brain in patients with major mental illness and may contribute to the pathology of these disorders. The magnitude of RNA oxidative damage may be associated with the severity of mental illness.

Increased systemic oxidatively generated DNA and RNA damage in schizophrenia

“…Furthermore, an increasing attention to RNA oxidation as an instigator of human aging and neuropathology is emerging (Nunomura et al, 2009). Interestingly, a recent post-mortem study found increased oxidation of RNA, but not of DNA, in the hippocampus of schizophrenia patients (Che et al, 2010). Similarly, we found a more pronounced difference in the RNA marker excretion (effect size (Cohen's d) ¼1.13) compared to the DNA marker excretion (Cohen's d¼0.69) in patients vs. controls.…”

Oxidation and nitration in dopaminergic areas of the prefrontal cortex from patients with bipolar disorder and schizophrenia

“…24 We used a 60× water immersion object ive and a confocal laser scanning microscope (CLSM; Olympus Fluoview FV1000, Olympus America Inc.) to capture images from 5 fields of each section, which were chosen by dividing the section into 5 equally sized rectangles, and imaging the middle region of each of the 5 rectangles. For CPM-and DAT-labelled sections, CPM was excited with the 405 nm laser (15% intensity) and Alexa488 was excited with the 488 nm laser (18% intensity).…”

Oxidative stress – assassin behind the ischemic stroke

“…Rajanikant G.K., Associate Professor, School of Biotechnology Coordinator, DBT -Bioinformatics Infrastructure Facility, National Institute of Technology Calicut, Calicut -673601, Kerala, India, phone: +91 495 228 5452, fax: +91 495 228 7250, e-mail: rajanikant@nitc.ac.in damage. As the brain consumes about 20% of the body's total oxygen, neuronal cells are more vulnerable than other cells to oxidative damage, although brain constitutes less than 2% of the total body weight [16]. The significance of oxidative damage as a component of many disease processes in the central nervous system (CNS) is being increasingly recognized.…”