title: Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants.
abstract: We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group,raphe magnusnucleus, lateral, and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas ~45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labeled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labeled for serotonin in the raphemagnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labeled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by (i) the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, (ii) the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and (iii) the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modeling the breathing network of premature infants.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Joubert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Loiseau
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et CliniqueParis, France; Sorbonne Paris Cité, Université Paris 13, EA2363 Hypoxie et PoumonsBobigny, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Perrin-Terrin
authors.affiliation: Institut de Neurosciences de la Timone, Aix Marseille Université, Centre National de la Recherche Scientifique, UMR 7289 Marseille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Cayetanot
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Frugière
authors.affiliation: Sorbonne Paris Cité, Université Paris 13, EA2363 Hypoxie et Poumons Bobigny, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voituron
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bodineau
keywords: PHOX2B; c-FOS; catecholamine; hypoxic ventilatory depression; serotonin; subcoeruleus nucleus