UPRES EA 3901, Faculté de Médecine, Université de Picardie Jules Verne, Amiens, F-80036, France.
Neuroscience. 2011 Oct 27;194:95-111. doi: 10.1016/j.neuroscience.2011.07.062. Epub 2011 Jul 31.
Acute hypoxia elicits a biphasic respiratory response characterized in the newborn by a transient hyperventilation followed by a severe decrease in respiratory drive known as hypoxic respiratory depression. Medullary O(2) chemosensitivity is known to contribute to respiratory depression induced by hypoxia, although precise involvement of cell populations remains to be determined. Having a thorough knowledge of these populations is of relevance because perturbations in the respiratory response to hypoxia may participate in respiratory diseases in newborns. We aimed to analyze the hypoxic response of ponto-medullary cell populations of kreisler mutant mice. These mice have defects in a gene expressed in two rhombomeres encompassing a part of the medulla oblongata implicated in hypoxic respiratory depression. Central responses to hypoxia were analyzed in newborn mice by measuring respiratory rhythm in ex vivo caudal pons-medullary-spinal cord preparations and c-fos expression in wild-type and kreisler mutants. The homozygous kreisler mutation, which eliminates most of rhombomere 5 and mis-specifies rhombomere 6, abolished (1) an early decrease in respiratory frequency within 10 min of hypoxia and (2) an intrinsic hypoxic activation, which is characterized by an increase in c-fos expression in the region of the ventral medullary surface encompassing the retrotrapezoid nucleus/parafacial respiratory group expressing Phox2b. This increase in c-fos expression persisted in wild-type Phox2b-negative and Phox2b-positive cells after blockade of synaptic transmission and rhythmogenesis by a low Ca(2+). Another central response was retained in homozygous kreisler mutant mice; it was distinguished by (1) a delayed (10-30 min) depression of respiratory frequency and (2) a downregulation of c-fos expression in the ventrolateral reticular nucleus of the medulla, the nucleus of the solitary tract, and the area of the A5 region. Thus, two types of ponto-medullary cell groups, with distinct anatomical locations, participate in central hypoxic respiratory depression in newborns.
急性缺氧会引起双相呼吸反应，在新生儿中表现为短暂的过度通气，随后呼吸驱动严重下降，称为缺氧性呼吸抑制。已知延髓氧化学敏感性有助于缺氧引起的呼吸抑制，尽管确切的细胞群参与仍有待确定。深入了解这些群体是相关的，因为对缺氧的呼吸反应的干扰可能参与新生儿的呼吸疾病。我们旨在分析 kreisler 突变小鼠桥延髓细胞群体的缺氧反应。这些小鼠在两个包含延髓中与缺氧性呼吸抑制有关的一部分的菱脑节中表达的基因存在缺陷。通过测量离体尾髓桥延髓脊髓标本中的呼吸节律和野生型和 kreisler 突变体中的 c-fos 表达，分析新生小鼠对缺氧的中枢反应。kreisler 纯合突变消除了大部分菱脑 5 并错误指定了菱脑 6，消除了 (1) 缺氧 10 分钟内呼吸频率的早期下降，以及 (2) 内在的缺氧激活，其特征是在延髓腹侧面包括表达 Phox2b 的 retrotrapezoid 核/拟面呼吸组的区域中 c-fos 表达增加。这种 c-fos 表达的增加在野生型 Phox2b 阴性和 Phox2b 阳性细胞中在突触传递和节律发生被低 Ca(2+) 阻断后仍然存在。在 homozygous kreisler 突变小鼠中保留了另一种中枢反应；它的特征是 (1) 呼吸频率的延迟 (10-30 分钟) 抑制，以及 (2) 延髓腹外侧网状核、孤束核和 A5 区域的 c-fos 表达下调。因此，两种类型的桥延髓细胞群，具有不同的解剖位置，参与新生儿中枢性缺氧性呼吸抑制。
