{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:57:58Z","timestamp":1787018278464,"version":"build-2736575974"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT081195MA"],"award-info":[{"award-number":["WT081195MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/12\/14\/29885"],"award-info":[{"award-number":["RG\/12\/14\/29885"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Modulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep and ascent to altitude, but the precise molecular mechanisms of this phenomenon remain controversial. Among the genes influenced by natural selection in high-altitude populations is one for the adenosine monophosphate\u2013activated protein kinase (AMPK) \u03b11-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated whether AMPK-\u03b11 and\/or AMPK-\u03b12 are required for the hypoxic ventilatory response and the mechanism of ventilatory dysfunctions arising from AMPK deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used plethysmography, electrophysiology, functional magnetic resonance imaging, and immediate early gene (c-fos) expression to assess the hypoxic ventilatory response of mice with conditional deletion of the AMPK-\u03b11 and\/or AMPK-\u03b12 genes in catecholaminergic cells, which compose the hypoxia-responsive respiratory network from carotid body to brainstem.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>AMPK-\u03b11 and AMPK-\u03b12 deletion virtually abolished the hypoxic ventilatory response, and ventilatory depression during hypoxia was exacerbated under anesthesia. Rather than hyperventilating, mice lacking AMPK-\u03b11 and AMPK-\u03b12 exhibited hypoventilation and apnea during hypoxia, with the primary precipitant being loss of AMPK-\u03b11 expression. However, the carotid bodies of AMPK-knockout mice remained exquisitely sensitive to hypoxia, contrary to the view that the hypoxic ventilatory response is determined solely by increased carotid body afferent input to the brainstem. Regardless, functional magnetic resonance imaging and c-fos expression revealed reduced activation by hypoxia of well-defined dorsal and ventral brainstem nuclei.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AMPK is required to coordinate the activation by hypoxia of brainstem respiratory networks, and deficiencies in AMPK expression precipitate hypoventilation and apnea, even when carotid body afferent input is normal.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201508-1667oc","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T19:26:03Z","timestamp":1450207563000},"page":"1032-1043","source":"Crossref","is-referenced-by-count":51,"title":["AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea"],"prefix":"10.1093","volume":"193","author":[{"given":"Amira D.","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophronia","family":"Lewis","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Juri\u010di\u0107","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utibe-Abasi","family":"Udoh","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurits A.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluseye A.","family":"Ogunbayo","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Puggioni","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Navarro-Dorado","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Foretz","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM U1016, Paris, France"},{"name":"CNRS UMR8104, Paris, France; and"},{"name":"Universit\u00e9 Paris Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Viollet","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM U1016, Paris, France"},{"name":"CNRS UMR8104, Paris, France; and"},{"name":"Universit\u00e9 Paris Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayank B.","family":"Dutia","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Marshall","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4650-7208","authenticated-orcid":false,"given":"A. 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