Oxidative damage to RNA but not DNA in the hippocampus of patients with major mental illness
Open accessAbstract
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.
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In major depressive disorder, higher oxidative stress, lower antioxidants, and oxidant-antioxidant imbalance are well documented in the hippocampus and medial prefrontal cortex, along with markers of DNA/RNA damage.
“increased oxidative stress, lower antioxidant levels, and imbalanced oxidant:antioxidant levels have been well documented within the hippocampus (103,104) and mPFC (104–106), resulting in associated markers of DNA/RNA damage in these regions.”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [103]
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- Authors
- Che, Y., Wang, J.-F., Shao, L., & Young, L. T.
- Affiliations
- University of British Columbia (CA)
- ORCID
- Young, L. Trevor
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2010-09
- Volume
- 35
- Issue
- 5
- Pages
- 296-302
- ISSN
- 1180-4882 (ISSN-L)
- PMC
- PMC2928282
- OpenAlex
- W2110790107
- Cited by
- 155
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 11 · 2018: 8 · 2017: 10 · 2016: 10 · 2015: 12 · 2014: 19 · 2013: 16 · 2012: 10
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- oxidative DNA damage, oxidative RNA damage, hippocampus, bipolar disorder, schizophrenia, major depressive disorder, 8-hydroxyguanosine, 8-hydroxy-2'-deoxyguanosine, postmortem brain, neuronal vulnerability
- MeSH terms
- Adult, Aged, Analysis of Variance, Bipolar Disorder, Depressive Disorder, Major, Major Depressive Disorder, DNA, Female, Hippocampus, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, RNA, Schizophrenia, Oxidative Stress
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