Altered Oxygen Metabolism Associated to Neurogenesis of Induced Pluripotent Stem Cells Derived From a Schizophrenic Patient
Altered Oxygen Metabolism Associated to Neurogenesis of Induced Pluripotent Stem Cells Derived From a Schizophrenic Patient
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DOI：
10.3727/096368911x600957
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Rehen, Stevens Kastrup
中科院分区：
文献类型：
--
作者：
Paulsen, Bruna da Silveira;Maciel, Renata de Moraes;Rehen, Stevens Kastrup
精神分裂症被定义为一种神经发育疾病，它会导致思想和感知过程的变化。还有情绪，通常会导致精神退化和情感迟钝。研究表明，精神分裂症患者细胞呼吸和氧化应激反应发生改变；然而，大部分的知识都是从死后的大脑分析或非神经细胞中获得的。在这里，我们描述了从精神分裂症患者的皮肤成纤维细胞产生的诱导多能干细胞中提取的神经细胞，与对照组相比，线粒体外耗氧量增加了两倍，活性氧（ROS）水平也升高了。这种ROS水平的差异被心境稳定剂丙戊酸逆转。我们的模型显示了神经发生过程中发生的代谢变化与精神分裂症相关的证据，有助于更好地了解疾病的发展，并突出了治疗和药物筛选的潜在靶点。
Schizophrenia has been defined as a neurodevelopmental disease that causes changes in the process of thoughts, perceptions. and emotions, usually leading to a mental deterioration and affective blunting. Studies have shown altered cell respiration and oxidative stress response in schizophrenia; however, most of the knowledge has been acquired from postmortem brain analyses or from nonneural cells. Here we describe that neural cells, derived from induced pluripotent stem cells generated from skin fibroblasts of a schizophrenic patient, presented a twofold increase in extramitochondrial oxygen consumption as well as elevated levels of reactive oxygen species (ROS), when compared to controls. This difference in ROS levels was reverted by the mood stabilizer valproic acid. Our model shows evidence that metabolic changes occurring during neurogenesis are associated with schizophrenia, contributing to a better understanding of the development of the disease and highlighting potential targets for treatment and drug screening.