Mechanisms and modulation of neural cell damage induced by oxidative stress
Mechanisms and modulation of neural cell damage induced by oxidative stress
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DOI：
10.1016/j.physbeh.2007.05.048
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发表时间：
2007-09-10
影响因子：
2.9
通讯作者：
Chen, Ming
中科院分区：
文献类型：
--
作者：
Ceccatelli, Sandra;Tamm, Christoffer;Chen, Ming
氧化应激与多种以神经元死亡为特征的神经退行性疾病有关。细胞凋亡和坏死是神经系统中细胞死亡的两种主要形式，诱导氧化应激的刺激可以导致这两种类型的死亡，具体取决于损伤的强度和持续时间。在本文中，我们报告了我们实验室的一系列研究，描述了分化神经元（例如小脑颗粒细胞和神经干细胞）中氧化应激激活的细胞内途径。使用体外/离体实验模型，我们研究了对损伤的敏感性是否会受到发育过程中发生的潜在损伤的影响。我们发现，产前接触高水平的糖皮质激素会使神经细胞（包括干细胞）对氧化应激损伤更加敏感。在子宫内接触甲基汞后也观察到类似的效果。行为分析已被证明是一种敏感的工具，可以检测早期刺激引起的轻微改变，这些改变会增加对氧化应激的易感性。我们的研究结果有助于理解早期事件如何通过改变细胞内过程而产生长期后果，这些过程使受影响的细胞容易出现功能障碍，而这种功能障碍可能会因随后遭受进一步的伤害而暴露或恶化。 (C) 2007 Elsevier Inc. 保留所有权利。
Oxidative stress has been linked to several neurodegenerative disorders characterized by neuronal death. Apoptosis and necrosis are the two major forms of cell death that have been described in the nervous system, and stimuli inducing oxidative stress can cause both types of death, depending on the intensity and the duration of the insult. In the present article, we report on a series of studies from our laboratory describing the intracellular pathways activated by oxidative stress in differentiated neurons, such as cerebellar granule cells, and neural stem cells. Using in vitro/ ex vivo experimental models, we have investigated whether the susceptibility to injuries can be affected by the occurrence of potential insults taking place during development. We have found that prenatal exposure to high levels of glucocorticoids renders neural cells, including stem cells, more sensitive to oxidative stress damage. Similar effects were seen after in utero exposure to methylmercury. The analysis of behavior has proven to be a sensitive tool to detect mild alterations induced by early stimuli that increase susceptibility to oxidative stress. Our findings contribute to the understanding of how early events may have long-term consequences by modifying intracellular processes that predispose the affected cells to dysfunction, which can be unmasked or worsen by subsequent exposure to further injuries. (C) 2007 Elsevier Inc. All rights reserved.