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

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

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J Psychiatry Neurosci 2010; 35(5): 296-302

Yi Che, PhD; Jun-Feng Wang, MD, PhD; Li Shao, MD, PhD; L. Trevor Young, MD, PhD

Che — Department of Physiology, Soochow University, People’s Republic of China; Wang, Shao, Young — Department of Psychiatry, University of British Columbia, Vancouver, BC

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.

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.


Submitted July 15, 2009; Revised Dec. 17, 2009, Feb. 3, 2010; Accepted Feb. 4, 2010.

Acknowledgments: This work was supported by grants from the Canadian Institutes of Health Research (L.T.Y. and J.-F.W.), Stanley Medical Research Institute (L.T.Y. and J.-F.W.) and National Alliance for Research on Schizophrenia and Depression Young Investigator Awards (J.-F.W.).

Competing interests: None declared.

Contributors: All authors designed the study. Dr. Che acquired the data, which he and Drs. Wang, and Young analyzed. Drs. Che, Wang
and Young wrote the article, which they and Dr. Shao reviewed. All authors approved the final version submitted for publication.

DOI: 10.1503/jpn.090083

Correspondence to: Dr. L.T. Young, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver BC V6T 2A1;
trevor.young@ubc.ca