{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:08:21Z","timestamp":1775275701050,"version":"3.50.1"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["Severo Ochoa Programme for Centres of Excellence"],"award-info":[{"award-number":["Severo Ochoa Programme for Centres of Excellence"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["PROMETEO\/2021\/031"],"award-info":[{"award-number":["PROMETEO\/2021\/031"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Physiological functions in mammals show circadian oscillations, synchronized by daily cycles of light and temperature. Central and peripheral clocks participate in this regulation. Since the ion channel TRPM8 is a critical cold sensor, we investigated its role in circadian function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used TRPM8 reporter mouse lines and TRPM8\u2010deficient mice. mRNA levels were determined by in situ hybridization or RT\u2010qPCR and protein levels by immunofluorescence. A telemetry system was used to measure core body temperature (Tc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TRPM8 is expressed in the retina, specifically in cholinergic amacrine interneurons and in a subset of melanopsin\u2010positive ganglion cells which project to the central pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. TRPM8\u2010positive fibres were also found innervating choroid and ciliary body vasculature, with a putative function in intraocular temperature, as shown in TRPM8\u2010deficient mice. Interestingly, <jats:italic>Trpm8<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> animals displayed increased expression of the clock gene <jats:italic>Per<\/jats:italic>2 and vasopressin (AVP) in the SCN, suggesting a regulatory role of TRPM8 on the central oscillator. Since SCN AVP neurons control body temperature, we studied Tc in driven and free\u2010running conditions. TRPM8\u2010deficiency increased the amplitude of Tc oscillations and, under dim constant light, induced a greater phase delay and instability of Tc rhythmicity. Finally, TRPM8\u2010positive fibres innervate peripheral organs, like liver and white adipose tissue. Notably, <jats:italic>Trpm8<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed a dysregulated expression of <jats:italic>Per<\/jats:italic>2 mRNA in these metabolic tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings support a function of TRPM8 as a temperature sensor involved in the regulation of central and peripheral clocks and the circadian control of Tc.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13896","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T16:55:22Z","timestamp":1666025722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The cold\u2010sensing ion channel <scp>TRPM8<\/scp> regulates central and peripheral clockwork and the circadian oscillations of body temperature"],"prefix":"10.1111","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-5267","authenticated-orcid":false,"given":"Alfonso","family":"Reim\u00fandez","sequence":"first","affiliation":[{"name":"Department of Physiology CIMUS, University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0726-3204","authenticated-orcid":false,"given":"Carlos","family":"Fern\u00e1ndez\u2010Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience. UMH\u2010CSIC  Alicante Spain"},{"name":"St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purificaci\u00f3n","family":"Ord\u00e1s","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience. UMH\u2010CSIC  Alicante Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9591-4144","authenticated-orcid":false,"given":"Pablo","family":"Hern\u00e1ndez\u2010Ortego","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience. UMH\u2010CSIC  Alicante Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6015-4680","authenticated-orcid":false,"given":"Rosal\u00eda","family":"Gallego","sequence":"additional","affiliation":[{"name":"Department of Morphological Sciences University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cruz","family":"Morenilla\u2010Palao","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience. UMH\u2010CSIC  Alicante Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Physiology CIMUS, University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8620-0588","authenticated-orcid":false,"given":"Francisco","family":"Mart\u00edn\u2010Cora","sequence":"additional","affiliation":[{"name":"Department of Physiology CIMUS, University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4623-2440","authenticated-orcid":false,"given":"Jos\u00e9 Lu\u00eds","family":"Pardo\u2010V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department Physiotherapy, Medicine and Biomedical Sciences CICA, University of A Coru\u00f1a  A Coru\u00f1a Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-5518","authenticated-orcid":false,"given":"Lindsay A.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Arce","sequence":"additional","affiliation":[{"name":"Department of Physiology CIMUS, University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1439-949X","authenticated-orcid":false,"given":"F\u00e9lix","family":"Viana","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience. UMH\u2010CSIC  Alicante Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-2609","authenticated-orcid":false,"given":"Rosa","family":"Se\u00f1ar\u00eds","sequence":"additional","affiliation":[{"name":"Department of Physiology CIMUS, University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.55.030193.000313"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135821"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-060909-153128"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020729"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067262"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.340"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069609"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11704"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-19-0153"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80959-9"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1449-15.2015"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-08-05681.1995"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)01145-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00129.2003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030351"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4133-04.2005"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050034"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/23328940.2015.1115803"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-19-08630.1999"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195262"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.622545"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05910"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.02.024"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3002-17.2018"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24694"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-018-2145-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3976-07.2008"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523811000344"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(83)91293-3"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.12.001"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11101877"},{"issue":"1","key":"e_1_2_8_33_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/IAE.0000000000003278","article-title":"Ocular surface temperature differences in retinal vascular diseases","volume":"42","author":"Naidorf\u2010Rosenblatt H","year":"2022","journal-title":"Retina"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00223-7"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199209000-00022"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M050724"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083602"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature719"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00652-9"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4578-07.2007"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.9.3414"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1991.32"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.18.4.249.5361"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24454"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198904"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:21:2:133"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748730406296749"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135919"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(83)91205-2"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00324-J"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2010.08.010"},{"issue":"12","key":"e_1_2_8_52_1","first-page":"2415","article-title":"Cold\u2010sensing TRPM8 channel participates in circadian control of the brown adipose tissue. Biochim Biophys acta, Mol","volume":"1864","author":"Moraes MN","year":"2017","journal-title":"Cell Res"},{"issue":"3","key":"e_1_2_8_53_1","first-page":"170","article-title":"The circadian system: a regulatory feedback network of periphery and brain","volume":"31","author":"Buijs FN","year":"2016","journal-title":"Phys Ther"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.183251.111"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00542.2012"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799890600637506"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.12.005"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20540"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(13)71055-7"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05137-7"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052475"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.08.003"},{"key":"e_1_2_8_63_1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos G","year":"2019"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1596-z"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0975"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.010173"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748730411414264"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13741"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.13896","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T09:55:03Z","timestamp":1692352503000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.13896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":67,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/apha.13896"],"URL":"https:\/\/doi.org\/10.1111\/apha.13896","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,31]]},"assertion":[{"value":"2022-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13896"}}