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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DOI：
10.1503/jpn.090083
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发表时间：
2010-09-01
影响因子：
4.3
通讯作者：
Young, L. Trevor
中科院分区：
文献类型：
--
作者：
Che, Yi;Wang, Jun-Feng;Young, L. Trevor
背景：中枢神经系统的氧化损伤越来越被认为是许多疾病的重要病理过程。以前，我们的实验室发现，在双相情感障碍和精神分裂症患者的死后脑组织中，脂质和蛋白质的氧化损伤增加。在目前的研究中，我们分析了双相情感障碍，精神分裂症和抑郁症患者死后海马组织的CA 1，CA 3和齿状回区域的核酸氧化损伤。研究方法：我们通过用识别RNA中的8-羟基-鸟苷和DNA中的8-羟基-2 '-脱氧鸟苷的单克隆抗体进行免疫组织化学来检查对核酸的氧化损伤。结果如下：我们发现，在双相情感障碍、精神分裂症和重度抑郁症患者中，海马CA 1、CA 3和齿状回区域的核酸氧化损伤量升高。这种损伤主要在细胞质中，表明损伤主要是RNA。与对照样本中的氧化损伤相比，精神分裂症患者的损伤程度较高，双相情感障碍患者的损伤程度较低，重度抑郁症患者的损伤程度较低。局限性：对我们结果的解释受到许多因素的限制，包括对患者病史的回顾性审查，相对较小的样本量以及包括药物滥用和死亡时正在接受各种药物治疗的患者。结论：我们的研究结果表明，氧化损伤的RNA，而不是DNA，发生在脆弱的神经元的大脑中的主要精神疾病患者，并可能有助于这些疾病的病理。RNA氧化损伤的程度可能与精神疾病的严重程度有关。
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.