Effects of Nocturnal Light on (Clock) Gene Expression in Peripheral Organs: A Role for the Autonomic Innervation of the Liver

BACKGROUND:The biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN), controls the daily rhythms in physiology and behavior. Early studies demonstrated that light exposure not only affects the phase of the SCN but also the functional activity of peripheral organs. More recently it was shown that the same light stimulus induces immediate changes in clock gene expression in the pineal and adrenal, suggesting a role of peripheral clocks in the organ-specific output. In the present study, we further investigated the immediate effect of nocturnal light exposure on clock genes and metabolism-related genes in different organs of the rat. In addition, we investigated the role of the autonomic nervous system as a possible output pathway of the SCN to modify the activity of the liver after light exposure. METHODOLOGY AND PRINCIPAL FINDINGS:First, we demonstrated that light, applied at different circadian times, affects clock gene expression in a different manner, depending on the time of day and the organ. However, the changes in clock gene expression did not correlate in a consistent manner with those of the output genes (i.e., genes involved in the functional output of an organ). Then, by selectively removing the autonomic innervation to the liver, we demonstrated that light affects liver gene expression not only via the hormonal pathway but also via the autonomic input. CONCLUSION:Nocturnal light immediately affects peripheral clock gene expression but without a clear correlation with organ-specific output genes, raising the question whether the peripheral clock plays a "decisive" role in the immediate (functional) response of an organ to nocturnal light exposure. Interestingly, the autonomic innervation of the liver is essential to transmit the light information from the SCN, indicating that the autonomic nervous system is an important gateway for the SCN to cause an immediate resetting of peripheral physiology after phase-shift inducing light exposures

Effect of Melatonin Implants during the Non-Breeding Season on the Onset of Ovarian Activity and the Plasma Prolactin in Dromedary Camel

To examine a possible control of reproductive seasonality by melatonin, continual-release subcutaneous melatonin implants were inserted 4.5 months before the natural breeding season (October–April) into female camels (Melatonin-treated group). The animals were exposed to an artificial long photoperiod (16L:8D) for 41 days prior to implant placement to facilitate receptivity to the short-day signal that is expected with melatonin implants. The treated and control groups (untreated females) were maintained separately under outdoor natural conditions. Ovarian follicular development was monitored in both groups by transrectal ultrasonography and by plasma estradiol-17β concentrations performed weekly for 8 weeks and then for 14 weeks following implant insertion. Plasma prolactin concentrations were determined at 45 and 15 days before and 0, 14, 28, 56, and 98 days after implant insertion. Plasma melatonin concentration was determined to validate response to the artificial long photoperiod and to verify the pattern of release from the implants. Results showed that the artificial long photoperiod induced a melatonin secretion peak of significantly (P < 0.05) shorter duration (about 2.5 h). Melatonin release from the implants resulted in higher circulating plasma melatonin levels during daytime and nighttime which persisted for more than 12 weeks following implants insertion. Treatment with melatonin implants advanced the onset of follicular growth activity by 3.5 months compared to untreated animals. Plasma estradiol-17β increased gradually from the second week after the beginning of treatment to reach significantly (P < 0.01) higher concentrations (39.2 ± 6.2 to 46.4 ± 4.5 pg/ml) between the third and the fifth week post insertion of melatonin implants. Treatment with melatonin implants also induced a moderate, but significant (P < 0.05) suppressive effect on plasma prolactin concentration on the 28th day. These results demonstrate that photoperiod appears to be involved in dromedary reproductive seasonality. Melatonin implants may be a useful tool to manipulate seasonality and to improve reproductive performance in this species. Administration of subcutaneous melatonin implants during the transition period to the breeding season following an artificial signal of long photoperiod have the potential to advance the breeding season in camels by about 2.5 months

Identification d’un nouveau signal de l’horloge circadienne chez les mammifères : le TGF-α

Les progrès récents ont permis d’identifier les mécanismes moléculaires responsables de la genèse des rythmes circadiens. Le mécanisme par lequel ce signal circadien, une fois construit, est distribué dans l’organisme reste encore à déterminer. Chez les mammifères, si la transmission du signal par une libération rythmique de neurotransmetteurs à partir des voies nerveuses efférentes est partiellement démontrée, la réalité d’une transmission humorale restait à prouver. Cela vient d’être fait avec l’identification du TGF-α

Forebrain oscillators ticking with different clock hands

Clock proteins like PER1 and PER2 are expressed in the brain, but little is known about their functionality outside the main suprachiasmatic clock. Here we show that PER1 and PER2 were neither uniformly present nor identically phased in forebrain structures of mice fed ad libitum. Altered expression of the clock gene Cry1 was observed in respective Per1 or Per2 mutants. In response to hypocaloric feeding, PERs timing was not markedly affected in few forebrain structures (hippocampus). In most other forebrain oscillators, including those expressing only PER1 (e.g., dorsomedial hypothalamus), PER2 (e.g., paraventricular hypothalamus) or both (e.g., paraventricular thalamus), PER1 was up-regulated and PER2 largely phase-advanced. Cry1 expression was selectively modified in the forebrain of Per mutants challenged with hypocaloric feeding. Our results suggest that there is not one single cerebral clock, but a system of multiple brain oscillators ticking with different clock hands and differentially sensitive to nutritional cues