RT Journal Article
T1 The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature
A1 Reimúndez Dubra, Alfonso
A1 Fernández Peña, Carlos
A1 Ordás, Purificación
A1 Hernández Ortego, Pablo
A1 Gallego Gómez, María Rosalía
A1 Morenilla Palao, Cruz
A1 Navarro, Juan
A1 Martín Cora, Francisco
A1 Pardo Vázquez, José Luis
A1 Schwarz, Lindsay A.
A1 Arce Vázquez, Víctor Manuel
A1 Viana, Félix
A1 Señarís Rodríguez, Rosa María
K1 Body temperature
K1 Central and peripheral clocks
K1 Circadian regulation
K1 Sensory physiology
K1 TRPM8
AB AimPhysiological 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.MethodsWe 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).ResultsTRPM8 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.ConclusionOur 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
PB Wiley
SN 1748-1708
YR 2022
FD 2022
LK http://hdl.handle.net/10347/30696
UL http://hdl.handle.net/10347/30696
LA eng
NO Reimúndez, A, Fernández-Peña, C, Ordás, P, et al. The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature. Acta Physiol. 2023; 237:e13896. doi: 10.1111/apha.13896
NO Ministerio de Ciencia e Innovación. Grant Number: Severo Ochoa Programme for Centres of Excellence Generalitat Valenciana. Grant Number: PROMETEO/2021/031Ministerio de Universidades. Grant Number: Margarita Salas postdoctoral fellowship to AR
DS Minerva
RD 23 abr 2026