{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:52:19Z","timestamp":1790193139634,"version":"4.1.0"},"reference-count":73,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL69064"],"award-info":[{"award-number":["R01 HL69064"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL148030"],"award-info":[{"award-number":["R01 HL148030"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["F31 HL145831"],"award-info":[{"award-number":["F31 HL145831"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR066082"],"award-info":[{"award-number":["R01 AR066082"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DK109570-01A1"],"award-info":[{"award-number":["1R01DK109570-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["T32 HL134621"],"award-info":[{"award-number":["T32 HL134621"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["F31 HL145831"],"award-info":[{"award-number":["F31 HL145831"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR066082"],"award-info":[{"award-number":["R01 AR066082"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DK109570-01A1"],"award-info":[{"award-number":["1R01DK109570-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007049","name":"Evelyn F. McKnight Brain Research Foundation","doi-asserted-by":"publisher","award":["BSCIRTF"],"award-info":[{"award-number":["BSCIRTF"]}],"id":[{"id":"10.13039\/100007049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:p> Circadian rhythms are endogenous and entrainable daily patterns of physiology and behavior. Molecular mechanisms underlie circadian rhythms, characterized by an ~24-h pattern of gene expression of core clock genes. Although it has long been known that breathing exhibits circadian rhythms, little is known concerning clock gene expression in any element of the neuromuscular system controlling breathing. Furthermore, we know little concerning gene expression necessary for specific respiratory functions, such as phrenic motor plasticity. Thus, we tested the hypotheses that transcripts for clock genes ( Bmal1, Clock, Per1, and Per2) and molecules necessary for phrenic motor plasticity ( Htr2a, Htr2b, Bdnf, and Ntrk2) oscillate in regions critical for phrenic\/diaphragm motor function via RT-PCR. Tissues were collected from male Sprague-Dawley rats entrained to a 12-h light-dark cycle at 4 zeitgeber times (ZT; n = 8 rats\/group): ZT5, ZT11, ZT17, and ZT23; ZT0\u2009=\u2009lights on. Here, we demonstrate that 1) circadian clock genes ( Bmal1, Clock, Per1, and Per2) oscillate in regions critical for phrenic\/diaphragm function, including the caudal medulla, ventral C3\u2013C5 cervical spinal cord, and diaphragm; 2) the clock protein BMAL1 is localized within CtB-labeled phrenic motor neurons; 3) genes necessary for intermittent hypoxia-induced phrenic\/diaphragm motor plasticity ( Htr2b and Bdnf) oscillate in the caudal medulla and ventral C3\u2013C5 spinal cord; and 4) there is higher intensity of immunofluorescent BDNF protein within phrenic motor neurons at ZT23 compared with ZT11 ( n = 11 rats\/group). These results suggest local circadian clocks exist in the phrenic motor system and confirm the potential for local circadian regulation of neuroplasticity and other elements of the neural network controlling breathing. <\/jats:p>","DOI":"10.1152\/ajpregu.00010.2020","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T22:12:42Z","timestamp":1588198362000},"page":"R1058-R1067","source":"Crossref","is-referenced-by-count":29,"title":["Circadian clock genes and respiratory neuroplasticity genes oscillate in the phrenic motor system"],"prefix":"10.1152","volume":"318","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-4327","authenticated-orcid":false,"given":"Mia N.","family":"Kelly","sequence":"first","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, Florida"},{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida"},{"name":"McKnight Brain Institute, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danelle N.","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Sunshine","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, Florida"},{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Ross","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, Florida"},{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Gumz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-1441","authenticated-orcid":false,"given":"Karyn A.","family":"Esser","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon S.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, Florida"},{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida"},{"name":"McKnight Brain Institute, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.09.014"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.01.007"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.006"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014523107"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1984.tb23452.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(96)00017-5"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nn1166"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-14-06239.2002"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4131-06.2007"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(85)90080-4"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.02.002"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-396971-2.00008-7"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/0748730405276352"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00012.2013"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.05.012"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5086-14.2015"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12085"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(84)90248-8"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3109\/07420528.2012.754447"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26557"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00346.2015"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00204.2017"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2336172100"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.11.009"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(00)00124-9"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00524.2010"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3353-09.2009"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00235.2015"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/bi500731f"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/1740-3391-1-2"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1993.265.4.R811"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2018.00032"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-009-0501-6"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-015-0039-5"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2014.00164"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.9.2.245"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/1740-3391-4-12"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2011.00052"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914112117"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2009.06.016"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00564.2014"},{"key":"B44","doi-asserted-by":"crossref","unstructured":"Mitchell GS. Respiratory Plasticity Following Intermittent Hypoxia: a Guide for Novel Therapeutic Approaches to Ventilatory Control Disorders? Boston, MA: Springer, 2007, p. 291\u2013311.","DOI":"10.1007\/978-0-387-70765-5_17"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.6.2466"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00523.2002"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-060909-153128"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.03.005"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2006.05.007"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2007.02.005"},{"key":"B51","first-page":"305","volume":"6","author":"Nelson W","year":"1979","journal-title":"Chronobiologia"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1161"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01079"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1080\/09291010600903692"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0096-9"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2015.12.006"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1113\/JP271436"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(00)00108-0"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(01)00316-4"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13455"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00683.x"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.6.1583"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00225.x"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0802-18.2018"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00152.2015"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00985.2012"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01113.2018"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.150"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.67"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00055.2011"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)90572-8"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.04.024"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.09.009"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308709101"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00010.2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T17:02:32Z","timestamp":1590685352000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpregu.00010.2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":73,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6,1]]}},"alternative-id":["10.1152\/ajpregu.00010.2020"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00010.2020","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]}}}