Trpv1 function in the mechanism of entrainment by temperature of peripheral clocks (#185)
The suprachiasmatic nucleus is considered the central clock because it is able to synchronize circadian rhythms, how it signals to all peripheral clocks is still unknown. Mammal core temperature (Tc) shows circadian rhythm of oscillation, which is controlled by the central clock. TRPV1 channels are sensitive to intrinsic temperature and are involved in the thermoregulation. We evaluated the role of TRPV1 antagonist, AMG-517, on the expression of TRPV1 and on the clock genes, Bmal1 and Per1 of adrenal and liver, as well as on the Tc. A jugular catheter and an abdominal temperature sensor were placed in adult male rats, housed at a 12:12 h light:dark cycle (light on at 7:00h). After 4 days, rats were treated i.v. with 128 nmol.Kg-¹ AMG 517 or vehicle at 7:00 h, time when telemetric Tc recordings showed the lowest Tc levels. This treatment induced an increase of Tc, which lasts about 50 minutes, indicating a role for TRPV1 channel on the maintenance of Tc. mRNA levels were measured by RT-qPCR, 1 h after the Tc peak induced by the antagonist. In adrenal, this treatment significantly increased Per1 and TRPV1 gene expressions, whereas no differences were detected in the Bmal1 expression. In the liver, it did not alter Per1 and TRPV1 while increased Bmal1 expression. Thus, the breakdown of circadian temperature variation affects Per1, Bmal1, and TRPV1 expressions, suggesting a role for temperature in the entrainment mechanism of peripheral clocks. In addition, in the liver, TRPV1 expression temporally varies with nadir levels at 19:00h (time when light was off), which coincides with lower Bmal1 and higher Per1 mRNA levels, suggesting that the clock molecular machinery may regulate the TRPV1 expression. TRPV1 may function as thermal sensor and signal circadian temperature variation to entrain peripheral clocks. Financial support: FAPEMIG, FAPESP, CNPq, CAPES, PRPq-UFMG