Chronic Intermittent Hypoxia Differentially Impacts Different States of Inspiratory Activity at the Level of the preBötzinger Complex.
Chronic Intermittent Hypoxia Differentially Impacts Different States of Inspiratory Activity at the Level of the preBötzinger Complex.
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DOI：
10.3389/fphys.2017.00571
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发表时间：
2017
影响因子：
4
通讯作者：
Ramirez JM
中科院分区：
文献类型：
--
作者：
Garcia AJ 3rd;Dashevskiy T;Khuu MA;Ramirez JM
前BötC复合体（preBötC）是一个延髓脑干网络，在不同吸气节律的产生中起关键作用。在分离的脑干切片中，preBötC重新配置以产生不同的节律，我们称之为基线条件下的"虚构正常呼吸"（即，碳）和缺氧时的"虚构喘息"。我们最近发现，暴露于慢性间歇性缺氧（CIH）后，虚构的正常呼吸是不规则的。然而，尚不清楚CIH如何影响虚构喘息。为了解决这个问题，从对照组和CIH暴露小鼠中制备含有preBötC的脑切片。在围缺氧间期获得了节律发生的电生理记录。我们研究了CIH如何影响节律的各个动态方面，其特征在于：（1）不规则性评分（IrS），以评估突发变异性;（2）波动值（χ），以量化整个时间序列中振荡的增益;以及（3）样本熵（sENT），以表征时间序列中振荡的模式/结构。在基础状态下，CIH增加了振幅的IrS（0.21 ± 0.2）和振幅的χ（0.34 ± 0.02），但不影响振幅的sENT。这表明CIH增加了爆发到爆发的不规则性和振幅波动的增益，但不影响振幅振荡的整体模式/结构。在过渡到缺氧，33%的控制节奏，而64%的CIH暴露的节奏没有表现出加倍的周期，这表明在过渡到缺氧的稳定的节奏发生的概率是更大的CIH。虽然29%的对照节律在整个缺氧期间保持节律性，但CIH暴露小鼠的所有切片在整个缺氧间隔期间均表现出节律。在缺氧期间，不再观察到组间振幅的χ差异。为了测试持续钠电流的贡献，我们研究了利鲁唑如何影响CIH后的节律发生。在暴露于CIH的网络中，利鲁唑降低了振幅的IrS（-24 ± 14%），但增加了周期的IrS（+49 ± 17%）。我们的数据表明，CIH影响preBötC，在某种程度上取决于氧合状态。沿着CIH对外周感觉器官的已知变化，CIH对preBötC的影响可能对睡眠呼吸暂停具有重要意义，睡眠呼吸暂停是一种以常氧和缺氧之间的快速转变为特征的疾病。
The preBötzinger complex (preBötC) is a medullary brainstem network crucially involved in the generation of different inspiratory rhythms. In the isolated brainstem slice, the preBötC reconfigures to produce different rhythms that we refer to as “fictive eupnea” under baseline conditions (i.e., carbogen), and “fictive gasping” in hypoxia. We recently demonstrated that fictive eupnea is irregular following exposure to chronic intermittent hypoxia (CIH). However, it is unknown how CIH impacts fictive gasping. To address this, brain slices containing the preBötC were prepared from control and CIH exposed mice. Electrophysiological recordings of rhythmogenesis were obtained during the perihypoxic interval. We examined how CIH affects various dynamic aspects of the rhythm characterized by: (1) the irregularity score (IrS), to assess burst-to-variability; (2) the fluctuation value (χ), to quantify the gain of oscillations throughout the time series; and (3) Sample Entropy (sENT), to characterize the pattern/structure of oscillations in the time series. In baseline conditions, CIH increased IrS of amplitude (0.21 ± 0.2) and χ of amplitude (0.34 ± 0.02) but did not affect sENT of amplitude. This indicated that CIH increased burst-to-burst irregularity and the gain of amplitude fluctuations but did not affect the overall pattern/structure of amplitude oscillations. During the transition to hypoxia, 33% of control rhythms whereas 64% of CIH-exposed rhythms showed no doubling of period, suggesting that the probability for stable rhythmogenesis during the transition to hypoxia was greater following CIH. While 29% of control rhythms maintained rhythmicity throughout hypoxia, all slices from CIH exposed mice exhibited rhythms throughout the hypoxic interval. During hypoxia, differences in χ for amplitude were no longer observed between groups. To test the contribution of the persistent sodium current, we examined how riluzole influenced rhythmogenesis following CIH. In networks exposed to CIH, riluzole reduced the IrS of amplitude (-24 ± 14%) yet increased IrS of period (+49 ± 17%). Our data indicate that CIH affects the preBötC, in a manner dependent on the state of the oxygenation. Along with known changes that CIH has on peripheral sensory organs, the effects of CIH on the preBötC may have important implications for sleep apnea, a condition characterized by rapid transitions between normoxia and hypoxia.
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DOI：
10.1523/jneurosci.4768-08.2009
发表时间：
2009-04-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Peng YJ;Nanduri J;Yuan G;Wang N;Deneris E;Pendyala S;Natarajan V;Kumar GK;Prabhakar NR
通讯作者：
Prabhakar NR
影响因子：
24
作者：
Javaheri S;Barbe F;Campos-Rodriguez F;Dempsey JA;Khayat R;Javaheri S;Malhotra A;Martinez-Garcia MA;Mehra R;Pack AI;Polotsky VY;Redline S;Somers VK
通讯作者：
Somers VK
影响因子：
25
作者：
Lieske, SP;Thoby-Brisson, M;Ramirez, JM
通讯作者：
Ramirez, JM
影响因子：
3.3
作者：
Peng, YJ;Rennison, J;Prabhakar, NR
通讯作者：
Prabhakar, NR
影响因子：
2.9
作者：
Di Fiore, J. M.;Poets, C. F.;MacFarlane, P.
通讯作者：
MacFarlane, P.