AUTHOR=Ramanantsoa Nelina , Matrot Boris , Vardon Guy , Lajard Anne-Marie , Voituron Nicolas , Dauger Stéphane , Denjean André , Hilaire Gérard , Gallego Jorge 

TITLE=Impaired Ventilatory and Thermoregulatory Responses to Hypoxic Stress in Newborn Phox2b Heterozygous Knock-Out Mice

JOURNAL=Frontiers in Physiology

VOLUME=2

YEAR=2011

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2011.00061

DOI=10.3389/fphys.2011.00061

ISSN=1664-042X

ABSTRACT=<p>The <italic>Phox2b</italic> 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 <italic>Phox2b</italic> 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<sub>2</sub>. To this end, we exposed 6-day-old <italic>Phox2b</italic><sup>+/−</sup> pups and their wild-type littermates (<italic>Phox2b</italic><sup>+/+</sup>) to hypoxia (10% O<sub>2</sub>) or hypercapnia (8% CO<sub>2</sub>) under thermoneutral (33°C) or cold (26°C) conditions. We found that <italic>Phox2b</italic><sup>+/−</sup> pups showed less normoxic ventilation (<italic>V</italic><sub>E</sub>) in the cold than <italic>Phox2b</italic><sup>+/+</sup> pups. <italic>Phox2b</italic><sup>+/−</sup> pups also showed lower oxygen consumption (VO<sub>2</sub>) 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 <italic>Phox2b</italic><sup>+/−</sup> pups. Finally, because serotonin (5-HT) neurons are pivotal to respiratory and thermoregulatory circuits and depend on <italic>Phox2b</italic> for their differentiation, we studied 5-HT metabolism using high pressure liquid chromatography, and found that it was altered in <italic>Phox2b</italic><sup>+/−</sup> pups. We conclude that <italic>Phox2b</italic> haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.</p>