精神分裂症的氧化应激:与神经化学致病假说的关系

G. Burbaeva, T. Prokhorova, O. Savushkina, E. Tereshkina, E. Vorobyeva, I. Boksha
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摘要

背景:精神分裂症的异质性体现在临床表现和生物学紊乱的多样性上,在此基础上提出了几种精神分裂症发病机制的神经化学假说。对目前精神分裂症发病机制假说的回顾表明,氧化应激不是疾病发展的主要原因,但会影响疾病的进程,并导致患者病情恶化。 目的:在疾病发病机制的神经化学假说框架内,分析氧化还原失衡和氧化应激与精神分裂症病理过程发展之间的关系。 材料与方法:使用关键词组合 "氧化应激"、"氧化还原失衡"、"精神分裂症"、"精神分裂症发病机制假说"、"抗氧化剂"、"神经递质"、"谷胱甘肽 "和 "神经炎症",在 Medline/PubMed 数据库、Scopus 和 RSCI 中进行了检索。 结论:对精神分裂症患者的大脑、血浆、血清和血细胞进行的大量研究以及对精神分裂症动物模型的研究数据表明,这种疾病存在氧化还原失衡和氧化应激。综上所述,这些数据表明,影响精神分裂症各种病理机制表现的遗传和环境因素(神经递质系统紊乱、N-甲基-D-天冬氨酸受体功能低下、神经炎症、信号蛋白磷酸化途径受损)会导致氧化应激,增强最初的病理变化,从而破坏大脑的同步过程和细胞间的交流。具有抗氧化和抗炎特性的药物、纠正线粒体功能障碍的化合物和 NMDAR 介导的信号调节剂可用作减少氧化应激有害影响的药物。这些药物对不同患者的疗效可能各不相同,因此开发生物标志物系统以识别更有可能对特定药物产生反应的个体具有重要意义。
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Oxidative Stress in Schizophrenia: Relation to Neurochemical Pathogenetic Hypotheses
   Background: heterogeneity of schizophrenia is reflected in the variety of clinical manifestations and biological disorders, on the basis of which several neurochemical hypotheses are formulated for schizophrenia pathogenesis. Review of the current hypotheses of schizophrenia pathogenesis shows that oxidative stress is not the main cause of the disease development, but affects its course and contributes to the deterioration of the patient’s condition.   Objective: analysis of the relationships between redox imbalance and oxidative stress and the development of pathological processes in schizophrenia within the framework of neurochemical hypotheses of the disease pathogenesis.   Material and methods: a search was made for sources in the Medline/PubMed databases, Scopus and RSCI using keyword combinations “oxidative stress”, “oxidation-reduction imbalance”, “schizophrenia”, “hypotheses of schizophrenia pathogenesis”, “antioxidants”, “neurotransmitters”, “glutathione”, “neuroinflammation”.   Conclusion: data from numerous studies of the brain of patients with schizophrenia, their blood plasma, serum, and blood cells as well as the study of animal models of schizophrenia indicate the presence of redox imbalance and oxidative stress in this disease. Taken together, these data indicate that genetic and environmental factors that affect the manifestation of various pathological mechanisms in schizophrenia (disturbances in neurotransmitter systems, hypofunction of N-methyl-D-aspartate receptors, neuroinflammation, impaired signaling protein phosphorylation pathways) lead to the oxidative stress, enhancing the initial pathological changes, as a result of which synchronization processes and intercellular communications in the brain become disrupted. Medicines with antioxidant and anti-inflammatory properties, compounds for correcting mitochondrial dysfunction, and NMDAR-mediated signaling modulators can be used as drugs to reduce the harmful effects of oxidative stress. The efficacy of these medicines may vary in different patients, so the development of biomarker systems aimed at identifying individuals who are more likely to respond to a particular drug is of great importance.
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