Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain
Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain
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DOI：
10.1016/j.freeradbiomed.2007.11.005
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发表时间：
2008-03-01
影响因子：
7.4
通讯作者：
Englander, Ella W.
中科院分区：
文献类型：
--
作者：
Lee, Heung M.;Greeley, George H., Jr.;Englander, Ella W.
胎盘功能不全和早产对神经发育的影响可以在啮齿动物新生儿缺氧的实验环境中建模。在这里，从出生后第3天（P3）开始，大鼠幼崽在低氧（9.5%）环境中饲养11天。与同龄正常缺氧饲养的对照组相比，这导致缺氧幼崽的脑和体重增加显著减少，这似乎反映了它们无法满足正常生长和发育的能量需求。旨在增强真核生物能量能力的适应性过程包括刺激线粒体生物发生。我们发现，在持续缺氧11天后，与正常缺氧条件相比，缺氧的P14幼犬大脑中的核呼吸因子-1和线粒体转录因子A水平升高，线粒体DNA （mtDNA）含量更高。相应的免疫组织化学分析显示，大皮质神经元中mtDNA密度增加，相比之下，在缺氧条件下饲养24小时（P3-P4）的幼鼠大脑中mtDNA含量没有变化。综上所述，这些数据表明，长时间的缺氧可能会触发神经元线粒体DNA含量的代偿性增加，以部分缓解发育中的缺氧大脑中能量稳态受损和能量能力下降。(c) 2007爱思唯尔公司版权所有。
The effects of placental insufficiency and preterm birth on neurodevelopment can be modeled in experimental settings of neonatal hypoxia in rodents. Here, rat pups were reared in reduced oxygen (9.5%) for 11 days, starting on postnatal day 3 (P3). This led to a significant reduction in brain and body weight gain in hypoxic pups compared to age-matched normoxia-reared controls, plausibly reflecting an inability to fulfill the energetic needs of normal growth and development. Adaptive processes designed to augment energetic capacity in eukaryotes include stimulation of mitochondrial biogenesis. We show that after 11 days of sustained hypoxia, the levels of nuclear respiratory factor-1 and mitochondrial transcription factor A are elevated and the content of mitochondrial DNA (mtDNA) is greater in the hypoxic P14 pup brain compared to normoxic conditions. Corresponding immunohistochemical analyses reveal increased density of mtDNA in large cortical neurons In contrast, no changes in mtDNA content are observed in the brain of pups reared for 24 h (P3-P4) under hypoxic conditions. Together, these data suggest that prolonged inadequate oxygenation may trigger a compensatory increase in neuronal mitochondrial DNA content to partially mitigate compromised energy homeostasis and reduced energetic capacity in the developing hypoxic brain. (c) 2007 Elsevier Inc. All rights reserved.