Respiratory long-term facilitation following intermittent hypoxia requires reactive oxygen species formation
Respiratory long-term facilitation following intermittent hypoxia requires reactive oxygen species formation
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DOI：
10.1016/j.neuroscience.2007.12.003
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发表时间：
2008-03-03
期刊：
影响因子：
3.3
通讯作者：
Mitchell, G. S.
中科院分区：
文献类型：
--
作者：
Macfarlane, P. M.;Mitchell, G. S.
急性间歇性低氧(AIH)引起一种称为长期促进(LTF)的呼吸可塑性。LTF是呼吸运动输出的进行性和持续性增加，表现为膈和舌下(XII)神经活动。由于ROS在多种形式的神经可塑性中起重要作用，而且间歇性低氧可增加ROS的产生，我们验证了ROS在AIH后的膈和XII LTF中是必需的假说。乌拉坦麻醉、麻痹、切断迷走神经和机械通气的SD大鼠暴露于AIH(11%O-2，3，5min发作，间隔5min)，监测AIH后60min的膈神经和XII神经活动。对照组大鼠虽然观察到了膈神经和XII LTF，但静脉注射。超氧阴离子清除剂四(1-甲基-4-吡啶)卟啉五氯锰(MnTMPyP)可剂量依赖地减弱二氢叶酸和XII长时程转铁。将MnTMPyP(5.5 mm；10亩L)局部应用于颈脊髓(C4)鞘内间隙，可消除隔膜，但不能消除XII LTF。因此，ROS在AIH诱导的呼吸性LTF中是必需的，而且相关的ROS似乎定位于呼吸运动核团附近，因为颈动脉注射MnTMPyP损害了膈(而不是XII)LTF。由于LTF依赖ROS存在于脊髓，因此它是一种新型的ROS依赖神经可塑性。爱思唯尔有限公司代表IBRO出版。
Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). LTF is a progressive and sustained increase in respiratory motor output as expressed in phrenic and hypoglossal (XII) nerve activity. Since reactive oxygen species (ROS) play important roles in several forms of neuroplasticity, and ROS production is increased by intermittent hypoxia, we tested the hypothesis that ROS are necessary for phrenic and XII LTF following AIH. Urethane-anesthetized, paralyzed, vagotomized and pump-ventilated Sprague - Dawley rats were exposed to AIH (11% O-2, 3, 5 min episodes, 5 min intervals), and both phrenic and XII nerve activity were monitored for 60 min post-AIH. Although phrenic and XII LTF were observed in control rats, i.v. manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), a superoxide anion scavenger, attenuated both phrenic and XII LTF in a dose dependent manner. Localized application of MnTMPyP (5.5 mM; 10 mu l) to the intrathecal space of the cervical spinal cord (C4) abolished phrenic, but not XII LTF. Thus, ROS are necessary for AIH-induced respiratory LTF, and the relevant ROS appear to be localized near respiratory motor nuclei since cervical MnTMPyP injections impaired phrenic (and not XII) LTF. Phrenic LTF is a novel form of ROS-dependent neuroplasticity since its ROS-dependence resides in the spinal cord. Published by Elsevier Ltd on behalf of IBRO.