Department of Physiology, Soochow University, People's Republic of China.
J Psychiatry Neurosci. 2010 Sep;35(5):296-302. doi: 10.1503/jpn.090083.
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.
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.
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.
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.
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.
中枢神经系统中的氧化损伤在许多疾病中被认为是一个重要的病理过程。以前，我们的实验室发现双相情感障碍和精神分裂症患者的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、精神分裂症和重度抑郁症患者死后海马组织 CA1、CA3 和齿状回区的核酸氧化损伤。
我们通过使用一种单克隆抗体进行免疫组织化学染色来检测核酸的氧化损伤，该抗体可识别 RNA 中的 8-羟基鸟嘌呤和 DNA 中的 8-羟基-2'-脱氧鸟嘌呤。
我们发现双相情感障碍、精神分裂症和重度抑郁症患者的海马 CA1、CA3 和齿状回区的核酸氧化损伤增加。这种损伤主要在细胞质中，表明损伤主要发生在 RNA 上。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中等，重度抑郁症患者的损伤程度较低。
我们的研究结果受到许多因素的限制，包括对患者病史的回顾性审查、样本量相对较小以及包括有物质滥用且在死亡时正在接受各种药物治疗的患者。
我们的研究结果表明，大脑中易受攻击的神经元发生了 RNA 氧化损伤，而不是 DNA 氧化损伤，这可能与这些疾病的病理学有关。RNA 氧化损伤的程度可能与精神疾病的严重程度有关。
