Breathing without CO(2) chemosensitivity in conditional Phox2b mutants

Autor: Muriel Thoby-Brisson, Jorge Gallego, Pierre-Louis Ruffault, Nelina Ramanantsoa, Julien Bouvier, Boris Matrot, Christo Goridis, Véronique Dubreuil, Gilles Fortin, Marie-Rose Hirsch, Jean-François Brunet
Přispěvatelé: Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie & Développement (N&D), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Fortin, Gilles, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Aging
medicine.medical_specialty
Survival
Peripheral chemoreceptors
Stimulation
Respiratory physiology
Congenital central hypoventilation syndrome
Biology
Mice
03 medical and health sciences
0302 clinical medicine
Pregnancy
Internal medicine
medicine
Animals
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Respiratory system
Alleles
Early Growth Response Protein 2
030304 developmental biology
Homeodomain Proteins
0303 health sciences
Respiration
General Neuroscience
Exons
Hypoventilation
Articles
Carbon Dioxide
medicine.disease
Immunohistochemistry
Sleep Apnea
Central
Electrophysiological Phenomena
Oxygen
Plethysmography
Endocrinology
Spinal Cord
Mutation
Breathing
Female
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Brainstem
Blood Gas Analysis
030217 neurology & neurosurgery
Homeostasis
Brain Stem
Transcription Factors
Zdroj: Journal of Neuroscience
Journal of Neuroscience, Society for Neuroscience, 2011, 31 (36), pp.12880-8. ⟨10.1523/JNEUROSCI.1721-11.2011⟩
Journal of Neuroscience, 2011, 31 (36), pp.12880-8. ⟨10.1523/JNEUROSCI.1721-11.2011⟩
ISSN: 0270-6474
1529-2401
DOI: 10.1523/JNEUROSCI.1721-11.2011⟩
Popis: Breathing is a spontaneous, rhythmic motor behavior critical for maintaining O2, CO2, and pH homeostasis. In mammals, it is generated by a neuronal network in the lower brainstem, the respiratory rhythm generator (Feldman et al., 2003). A century-old tenet in respiratory physiology posits that the respiratory chemoreflex, the stimulation of breathing by an increase in partial pressure of CO2in the blood, is indispensable for rhythmic breathing. Here we have revisited this postulate with the help of mouse genetics. We have engineered a conditional mouse mutant in which the toxicPHOX2B27Alamutation that causes congenital central hypoventilation syndrome in man is targeted to the retrotrapezoid nucleus, a site essential for central chemosensitivity. The mutants lack a retrotrapezoid nucleus and their breathing is not stimulated by elevated CO2at least up to postnatal day 9 and they barely respond as juveniles, but nevertheless survive, breathe normally beyond the first days after birth, and maintain blood PCO2within the normal range. Input from peripheral chemoreceptors that sense PO2in the blood appears to compensate for the missing CO2response since silencing them by high O2abolishes rhythmic breathing. CO2chemosensitivity partially recovered in adulthood. Hence, during the early life of rodents, the excitatory input normally afforded by elevated CO2is dispensable for life-sustaining breathing and maintaining CO2homeostasis in the blood.
Databáze: OpenAIRE
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