title: The central chemosensitivity is not altered by cerebral erythropoietin.
abstract: The stimulation of central chemoreceptors by CO2 is considered essential for breathing. The supporting evidence include the fact that central apnea in neonates correlates with immaturity of the CO2-sensing mechanism, and that congenital central hypoventilation syndrome (CCHS) is characterized by the absence of a ventilatory response to elevated PCO2. We reported previously that cerebral erythropoietin (Epo) is a potent respiratory stimulant upon normoxia and hypoxia. The injection of soluble Epo receptor (sEpoR; the natural EpoR competitor to bind Epo) via the cisterna magna (ICI: intra-cisternal injection) decreases basal ventilation in adult and newborn mice. Moreover, sEpoR induces respiratory depression in adult and newborn mice exposed to hypoxia. In this study we tested the hypothesis that endogenous brain Epo also modulates the respiratory stimulation induced by the activation of central CO2 chemoreceptors. Adult and newborn male and female mice received an injection of sEpoR or vehicle via the cisterna magna. Twenty-four hours later basal minute ventilation and the ventilatory response to hypercapnia (5% CO2) were evaluated by plethysmography. Our results did not show a difference in the hypercapnic response between sEpoR and vehicle-injected male or female mice at postnatal or adult ages. We concluded that endogenous brain Epo does not contribute to modulating the PCO2-mediated central activation of breathing.
authors.affiliation: Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, QC, Canada.
authors.forename: Orlane
authors.initials: O
authors.lastname: Ballot
authors.affiliation: Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, QC, Canada.
authors.forename: Sofien
authors.initials: S
authors.lastname: Laouafa
authors.affiliation: Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, QC, Canada; Molecular biology and Biotechnology Institute, Universidad Mayor de San Andres, La Paz, Bolivia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Elliot-Portal
authors.affiliation: Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, QC, Canada.
authors.forename: Rose
authors.initials: R
authors.lastname: Tam
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, UFR SMBH, Laboratoire "Hypoxie et poumons", EA 2363, 93017, Bobigny, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voituron
authors.affiliation: Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, QC, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Joseph
authors.affiliation: Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, QC, Canada. Electronic address: jorge.soliz@crchuq.ulaval.ca.
authors.forename: Jorge
authors.initials: J
authors.lastname: Soliz
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000494:pharmacology; D002946:Cisterna Magna; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000494:pharmacology; D017467:Receptors, Erythropoietin / Q000008:administration & dosage; D012119:Respiration
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D002245:Carbon Dioxide; D010100:Oxygen
keywords: Central chemosensitivity; Erythropoietin; Hypercapnia; Newborn and adult mice; Respiration; Sex dimorphism; Soluble erythropoietin receptor