Sinalização da variação de temperatura corporal interna para o relógio biológico via canais TRPV1

Abstract

Circadian oscillations in core temperature have been proposed as an important synchronizer of peripheral clocks, but the mechanism is still unclear. It is believed that transient receptor of potential vanilloid channel (TRPV1) participates on peripheral thermal perception. Thus, we hypothesize that this channel is involved in circadian temperature perception. We evaluated, in adult rats, the effects of blockage and of desensitization of TRPV1 on clock gene expression in suprachiasmatic nucleus (SCN, central clock) and peripheral tissues, on core temperature (Tcore) and on spontaneous locomotor activity (SLA). Tcore and SLA were registered by telemetry. A group of animals was injected i.v. with AMG-517 antagonist and another group was injected i.p. with TRPV1 agonist, resiniferatoxin (RTX) in a sufficient dose to desensitize these channels in abdominal cavity. Animals were injected with corresponding vehicles as a control. After infusion of AMG-517, Tcore were elevated at 20, 30, 40, 80, 90 e 100 minutes compared to vehicle group. Each animal was euthanized 1 hour after the first elevated Tcore. RTX-treated animals or vehicle were euthanized in zeitgeber (ZT) 0 (lights on), 6, 12, 18. Circadian rhythm of core temperature and spontaneous locomotor activity showed a decrease in the amplitude and an advance locomotor activity onset in desensitized animals. Clock genes’ RNAm rPer1, rBmal1 and TRPV1 were analyzed using qPCR in liver, adrenal and in microdissections of SCN. In liver, AMG-517 increased rBmal1 while in adrenal, it increased rPer1. These results point to a role for TRPV1 on the clock entrainment mechanism. RTX blocked circadian rhythm of rPer1 and rBmal1 in adrenal where as in liver only of rPer1. The lack of TRPV1channel function generates an alteration on circadian rhythm of core temperature and expression of clock genes, suggesting that this channel may be critical for signaling of temperature rhythm to peripheral clocks. After blockade of TRPV1 channels, it was also observed a reduction in serum concentrations of corticosterone, which could occur as consequence of the disruption of systemic biological clock or adrenal’s local clock.