Role of oxidative stress in the pathogenesis of autism spectrum disorders

Svetlana G. Belokoskova, Sergey G. Tsikunov
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Abstract

The literature review reflects the contemporary information on the role of oxidative stress in the pathogenesis of autism spectrum disorders. We present data on the importance of genetic predisposition, environmental factors, and epigenetic influences on the development of oxidative stress, which, during critical periods of early brain development, may influence the induction and progression of the disease. The role of mitochondrial dysfunction, immunological disorders, increased permeability of the blood-brain barrier, hypoperfusion of the brain causing or aggravating the redox imbalance in patients with autism spectrum disorders is shown. Analysis of the literature data indicates that the increased content of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione, ceruloplasmin and transferrin in the blood and brain of patients with autism spectrum disorders reflects the activation of compensatory mechanisms. Increased levels of malondialdehyde, xanthine oxidase, nitric oxide in various biological media indicate insufficiency of antioxidant protection system. Taking into account the role of oxidative stress in the pathogenesis of autism spectrum disorders, therapy including antioxidant drugs is indicated for correction of metabolic disorders.
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氧化应激在自闭症谱系障碍发病机制中的作用
文献综述反映了氧化应激在自闭症谱系障碍发病机制中的作用的当代信息。我们提出了遗传易感性、环境因素和表观遗传对氧化应激发展的重要性的数据,在早期大脑发育的关键时期,氧化应激可能影响疾病的诱导和进展。线粒体功能障碍、免疫障碍、血脑屏障通透性增加、脑灌注不足导致或加重自闭症谱系障碍患者氧化还原失衡的作用。对文献资料的分析表明,自闭症谱系障碍患者血液和大脑中超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、谷胱甘肽、铜蓝蛋白和转铁蛋白含量的升高反映了代偿机制的激活。各种生物培养基中丙二醛、黄嘌呤氧化酶、一氧化氮水平升高表明抗氧化保护系统不足。考虑到氧化应激在自闭症谱系障碍发病机制中的作用,包括抗氧化药物在内的治疗被用于纠正代谢紊乱。
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