INSERM, UMR 676, Robert Debré Hospital Paris, France.
Front Physiol. 2011 Sep 23;2:61. doi: 10.3389/fphys.2011.00061. eCollection 2011.
The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O(2). To this end, we exposed 6-day-old Phox2b(+/-) pups and their wild-type littermates (Phox2b(+/+)) to hypoxia (10% O(2)) or hypercapnia (8% CO(2)) under thermoneutral (33°C) or cold (26°C) conditions. We found that Phox2b(+/-) pups showed less normoxic ventilation (V(E)) in the cold than Phox2b(+/+) pups. Phox2b(+/-) pups also showed lower oxygen consumption (VO(2)) in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b(+/-) pups. Finally, because serotonin (5-HT) neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high pressure liquid chromatography, and found that it was altered in Phox2b(+/-) pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.
Phox2b 对于自主神经系统的发育是必要的，尤其是对于呼吸神经元回路的发育。在本研究中，我们研究了 Phox2b 在对低氧应激的通气和体温调节反应中的作用，这在出生后期间是密切相关的。低氧应激是通过强烈的热刺激与减少吸入 O(2) 结合或不结合产生的。为此，我们使 6 天大的 Phox2b(+/-) 幼崽及其野生型同窝仔（Phox2b(+/+)）在热中性（33°C）或寒冷（26°C）条件下暴露于低氧（10% O(2)) 或高碳酸血症（8% CO(2)) 中。我们发现 Phox2b(+/-) 幼崽在寒冷中表现出比 Phox2b(+/+) 幼崽更低的常氧通气（V(E))。Phox2b(+/-) 幼崽在寒冷中也表现出较低的氧气消耗（VO(2))，反映出减少的产热和较低的体温。此外，虽然低温抑制了两组基因型的低氧和高碳酸血症的通气反应，但在 Phox2b(+/-) 幼崽中这种影响不那么明显。最后，因为 5-羟色胺（5-HT）神经元对于呼吸和体温调节回路是至关重要的，并且依赖于 Phox2b 分化，我们使用高效液相色谱法研究了 5-HT 代谢，并发现 Phox2b(+/-) 幼崽中的 5-HT 代谢发生了改变。我们得出结论，Phox2b 杂合不足改变了新生儿应对代谢挑战的能力，这可能是由于 5-HT 信号转导受损所致。
