Oxygen causes cell death in the developing brain
Oxygen causes cell death in the developing brain
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DOI：
10.1016/j.nbd.2004.07.019
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发表时间：
2004-11-01
影响因子：
6.1
通讯作者：
Ikonomidou, C
中科院分区：
文献类型：
--
作者：
Felderhoff-Mueser, U;Bittigau, P;Ikonomidou, C
早产幸存者的神经系统发病率很高。即使没有补充氧气，早产儿也会暴露在比宫内情况高四倍的氧分压下。在这里，我们报告了短时间暴露于非生理性氧气水平会引发幼年啮齿类动物大脑中的神经细胞凋亡性变性。对氧气神经毒性的脆弱性仅限于生命的头两周，这是一个以快速生长为特征的时期，人类的这一时期从怀孕第六个月扩展到生命的第三年。氧引起氧化应激，神经营养因子表达减少，生存信号蛋白RAS、细胞外信号调节激酶(ERK 1/2)和蛋白激酶B(Akt)失活。在大脑中过度表达组成性激活的RAS和磷酸化的ERK1/2的SynRas转基因小鼠可以抵抗氧神经毒性。我们的发现揭示了一种可能潜在地损害人类早产儿发育中的大脑的机制。(C)2004 Elsevier Inc.保留所有权利。
Substantial neurologic morbidity occurs in survivors of premature birth. Premature infants are exposed to partial oxygen pressures that are fourfold higher compared to intrauterine conditions, even if no supplemental oxygen is administered. Here we report that short exposures to nonphysiologic oxygen levels can trigger apoptotic neurodegeneration in the brains of infant rodents. Vulnerability to oxygen neurotoxicity is confined to the first 2 weeks of life, a period characterized by rapid growth, which in humans expands from the sixth month of pregnancy to the third year of life. Oxygen caused oxidative stress, decreased expression of neurotrophins, and inactivation of survival signaling proteins Ras, extracellular signal-regulated kinase (ERK 1/2), and protein kinase B (Akt). The synRas-transgenic mice overexpressing constitutively activated Ras and phosphorylated kinases ERK1/2 in the brain were protected against oxygen neurotoxicity. Our findings reveal a mechanism that could potentially damage the developing brain of human premature neonates. (C) 2004 Elsevier Inc. All rights reserved.