title: PI3K and MEK1/2 molecular pathways are involved in the erythropoietin-mediated regulation of the central respiratory command.
abstract: Erythropoietin stimulation modulates the central respiratory command in newborn mice. Specifically, the central respiratory depression induced by hypoxia is attenuated by acute (1h) or abolished by chronic erythropoietin stimulation. However, the underlying mechanisms remain unknown. As MEK and PI3K pathways are commonly involved in Epo-mediated effects of neuroprotection and erythropoiesis, we investigated here the implication of PI3K and MEK1/2 in the Epo-mediated regulation of the central respiratory command. To this end, in vitro brainstem-spinal cord preparations from 3 days old transgenic (Tg21; constitutively overexpressing erythropoietin in the brain specifically) and control mice were used. Our results show that blockade of PI3K or MEK1/2 stimulates normoxic bursts frequency in Tg21 preparations and abolish hypoxia-induced frequency depression in control preparations. These results show that MEK1/2 and PI3K pathways are involved in the Epo-mediated regulation of the central respiratory command. Moreover, this is the first demonstration that MEK1/2 and PI3K are involved in the brainstem central respiratory command.
authors.affiliation: Department of Pediatrics, Laval University, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Hôpital St-François d'Assise, 10 Rue de l'Espinay, Québec, QC G1L 3L5, Canada. Electronic address: celine.caravagna.1@ulaval.ca.
authors.forename: Céline
authors.initials: C
authors.lastname: Caravagna
authors.affiliation: Department of Pediatrics, Laval University, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Hôpital St-François d'Assise, 10 Rue de l'Espinay, Québec, QC G1L 3L5, Canada. Electronic address: Jorge.soliz@crchuq.ulaval.ca.
authors.forename: Jorge
authors.initials: J
authors.lastname: Soliz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002070:Butadienes / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D009570:Nitriles; C113580:U 0126; D004921:Erythropoietin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse
keywords: Central respiratory command; Electrophysiology; Erythropoietin; Hypoxia