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The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature
dc.contributor.author | Reimúndez, Alfonso | |
dc.contributor.author | Fernández-Peña, Carlos | |
dc.contributor.author | Ordás, Purificación | |
dc.contributor.author | Hernández-Ortego, Pablo | |
dc.contributor.author | Gallego, Rosalía | |
dc.contributor.author | Morenilla-Palao, Cruz | |
dc.contributor.author | Navarro, Juan | |
dc.contributor.author | Martín-Cora, Francisco | |
dc.contributor.author | Pardo-Vázquez, José L. | |
dc.contributor.author | Schwartz, Lindsay A. | |
dc.contributor.author | Arce, Víctor | |
dc.contributor.author | Viana, Félix | |
dc.contributor.author | Señarís, Rosa | |
dc.date.accessioned | 2023-01-16T12:07:18Z | |
dc.date.available | 2023-01-16T12:07:18Z | |
dc.date.issued | 2022-10-17 | |
dc.identifier.citation | Reimúndez A, Fernández-Peña C, Ordás P, Hernández-Ortego P, Gallego R, Morenilla-Palao C, Navarro J, Martín-Cora F, Pardo-Vázquez JL, Schwarz LA, Arce V, Viana F, Señarís R. The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature. Acta Physiol (Oxf). 2023 Mar;237(3):e13896. | es_ES |
dc.identifier.issn | 1748-1708 | |
dc.identifier.uri | http://hdl.handle.net/2183/32355 | |
dc.description.abstract | [Abstract] Aim: 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. Methods: We used TRPM8 reporter mouse lines and TRPM8-deficient mice. mRNA levels were determined by in situ hybridization or RT-qPCR and protein levels by immunofluorescence. A telemetry system was used to measure core body temperature (Tc). Results: TRPM8 is expressed in the retina, specifically in cholinergic amacrine interneurons and in a subset of melanopsin-positive ganglion cells which project to the central pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. TRPM8-positive fibres were also found innervating choroid and ciliary body vasculature, with a putative function in intraocular temperature, as shown in TRPM8-deficient mice. Interestingly, Trpm8-/- animals displayed increased expression of the clock gene Per2 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-running conditions. TRPM8-deficiency increased the amplitude of Tc oscillations and, under dim constant light, induced a greater phase delay and instability of Tc rhythmicity. Finally, TRPM8-positive fibres innervate peripheral organs, like liver and white adipose tissue. Notably, Trpm8-/- mice displayed a dysregulated expression of Per2 mRNA in these metabolic tissues. Conclusion: 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. | es_ES |
dc.description.sponsorship | This study was supported by the Projects RT2018-099995-B100 to RS and AEI/10.13039/501100011033 to FV (Spanish Ministry of Science and Innovation), co-financed by Generalitat Valenciana (PROMETEO/2021/031) and the Severo Ochoa Programme for Centres of Excellence in R&D (ref. SEV-2017-0723). PO held predoctoral fellowship of MINECO (BES-2011-047063). AR holds a Margarita Salas post-doctoral fellowship (Spanish Ministry of Universities). | es_ES |
dc.description.sponsorship | Ministerio de Ciencia e Innovación (España); RT2018-099995-B100 | es_ES |
dc.description.sponsorship | Generalitat Valenciana; PROMETEO/2021/031 | es_ES |
dc.description.sponsorship | info:eu-repo/grantAgreement/MICINN/Programa Estatal de Promoción del Talento y su Empleabilidad/BES-2011-047063/ES | es_ES |
dc.description.sponsorship | Ministerio de Ciencia e Innovación (España); AEI/10.13039/501100011033 | |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation.uri | https://doi.org/10.1111/apha.13896 | es_ES |
dc.rights | Creative Commons Attribution-NonCommercial 4.0 International License (CC-BY-NC 4.0) | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | * |
dc.subject | TRPM8 | es_ES |
dc.subject | Body temperature | es_ES |
dc.subject | Central and peripheral clocks | es_ES |
dc.subject | Circadian regulation | es_ES |
dc.subject | Sensory physiology | es_ES |
dc.title | The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | Acta Physiologica | es_ES |
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