Nitric oxide synthase and intermittent hypoxia-induced spatial learning deficits in the rat
Nitric oxide synthase and intermittent hypoxia-induced spatial learning deficits in the rat
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DOI：
10.1016/j.nbd.2004.05.006
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发表时间：
2004-10-01
影响因子：
6.1
通讯作者：
Gozal, D
中科院分区：
文献类型：
--
作者：
Li, RC;Row, BW;Gozal, D
睡眠中的间歇性缺氧（IH）可导致大鼠显著的神经行为缺陷。由于一氧化氮（NO）与缺血-再灌注相关的病理生理学后果有关，因此在Sprague-Dawley大鼠皮层中检查了睡眠期间IH（每90 s交替21%和10%O-2）和持续缺氧（SH; 10%O-2）对脑中一氧化氮合酶（NOS）亚型诱导的时间效应，持续缺氧长达14天。内皮型一氧化氮合酶（eNOS）和神经型一氧化氮合酶（nNOS）在两组均无明显变化。同样，诱导型NOS（iNOS）不受SH的影响。然而，在IH的第1天和第3天观察到iNOS的表达和活性增加（与对照相比P < 0.01; n = 12/组），并且随后在第7天和第14天恢复到基础水平。此外，IH介导的神经行为缺陷在水迷宫中显着减弱iNOS基因敲除小鼠。我们的结论是，IH与时间依赖性诱导的iNOS和iNOS的表达增加可能发挥关键作用的早期病理生理事件，导致IH介导的神经行为缺陷。(C)2004年爱思唯尔公司All rights reserved.
Intermittent hypoxia (IH) during sleep induces significant neurobehavioral deficits in the rat. Since nitric oxide (NO) has been implicated in ischemia-reperfusion-related pathophysiological consequences, the temporal effects of IH (alternating 21% and 10% O-2 every 90 s) and sustained hypoxia (SH; 10% O-2) during sleep for up to 14 days on the induction of nitric oxide synthase (NOS) isoforms in the brain were examined in the cortex of Sprague-Dawley rats. No significant changes of endothelial NOS (eNOS) and neuronal NOS (nNOS) occurred over time with either IH or SH. Similarly, inducible NOS (iNOS) was not affected by SH. However, increased expression and activity of iNOS were observed on days 1 and 3 of IH (P < 0.01 vs. control; n = 12/group) and were followed by a return to basal levels on days 7 and 14. Furthermore, IH-mediated neurobehavioral deficits in the water maze were significantly attenuated in iNOS knockout mice. We conclude that IH is associated with a time-dependent induction of iNOS and that the increased expression of iNOS may play a critical role in the early pathophysiological events leading to IH-mediated neurobehavioral deficits. (C) 2004 Elsevier Inc. All rights reserved.