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

Le contrôle environnemental et neuroendocrinien de l’activité saisonnière de la reproduction chez le dromadaire

Le dromadaire (Camelus dromedarius), qui est un mammifère bien adapté au désert est une espèce à reproduction saisonnière. Sa saison sexuelle a lieu durant l’hiver et le printemps. Ces périodes coïncident avec l’abondance des ressources alimentaires et des conditions climatiques favorables pour la survie de la progéniture. Toutefois les mécanismes impliqués dans le contrôle de cette saisonnalité restent encore mal élucidés. L’objectif de cette revue est de décrire les caractéristiques de la reproduction chez le dromadaire. Cela inclue la distribution géographique de sa saison sexuelle et son déclenchement possible par plusieurs paramètres environnementaux physiques, notamment la température ambiante, la photopériode et la quantité de précipitations. De plus, plusieurs aspects de cette saisonnalité ont été discutés chez le mâle et la femelle. Finalement, cette revue analyse les facteurs neuroendocriniens impliqués dans la saisonnalité de reproduction, notamment, le rôle putatif de deux neuropeptides hypothalamiques, le kisspeptin et le (Arg) (Phe) peptide apparenté. Mots-clés: Dromadaire, saisonnalité de reproduction, précipitations, photopériode, température ambiante, disponibilité alimentaire, kisspeptin, RFRP. The dromedary camel (Camelus dromedarius), a well-adapted desert mammal, is a seasonal breeder whose sexual activity occurs during the winter and spring. These periods coincide with food resources and climate conditions are favorable for offspring’s survival. The mechanisms involved in the control of this seasonality however still need to be elucidated. The aim of this review is to describe the reproductive patterns of the dromedary camel. This includes the geographical seasonal breeding distribution of this species taking into account the role of various physical environmental parameters notably temperature, day length and the amount of rainfall. Further, various aspects of seasonal breeding in male and female camels are discussed as well as the neuroendocrine factors that may control seasonal such phenomena. Finally, the putative roles of two hypothalamic neuropeptides, kisspeptin and (Arg) (Phe) related peptide, are proposed for the control of camel’s seasonal reproduction. Keywords: Dromedary camel, seasonal breeding, rainfall, photoperiod, ambient temperature, food availability, Kisspeptin, RFRP

Environmental and neuroendocrine control of breeding activity in the dromedary camel

The dromedary camel (Camelus dromedarius), a well-adapted desert mammal, is a seasonal breeder whose sexual activity occurs during the winter and spring. These periods coincide with food resources and climate conditions are favorable for offspring’s survival. The mechanisms involved in the control of this seasonality however still need to be elucidated. The aim of this review is to describe the reproductive patterns of the dromedary camel. This includes the geographical seasonal breeding distribution of this species taking into account the role of various physical environmental parameters notably temperature, day length and the amount of rainfall. Further, various aspects of seasonal breeding in male and female camels are discussed as well as the neuroendocrine factors that may control seasonal such phenomena. Finally, the putative roles of two hypothalamic neuropeptides, kisspeptin and (Arg) (Phe) related peptide, are proposed for the control of camel’s seasonal reproduction

Ancestral TSH mechanism signals summer in a photoperiodic mammal

SummaryIn mammals, day-length-sensitive (photoperiodic) seasonal breeding cycles depend on the pineal hormone melatonin, which modulates secretion of reproductive hormones by the anterior pituitary gland [1]. It is thought that melatonin acts in the hypothalamus to control reproduction through the release of neurosecretory signals into the pituitary portal blood supply, where they act on pituitary endocrine cells [2]. Contrastingly, we show here that during the reproductive response of Soay sheep exposed to summer day lengths, the reverse applies: Melatonin acts directly on anterior-pituitary cells, and these then relay the photoperiodic message back into the hypothalamus to control neuroendocrine output. The switch to long days causes melatonin-responsive cells in the pars tuberalis (PT) of the anterior pituitary to increase production of thyrotrophin (TSH). This acts locally on TSH-receptor-expressing cells in the adjacent mediobasal hypothalamus, leading to increased expression of type II thyroid hormone deiodinase (DIO2). DIO2 initiates the summer response by increasing hypothalamic tri-iodothyronine (T3) levels. These data and recent findings in quail [3] indicate that the TSH-expressing cells of the PT play an ancestral role in seasonal reproductive control in vertebrates. In mammals this provides the missing link between the pineal melatonin signal and thyroid-dependent seasonal biology

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

Effects of muscarinic receptor stimulation on Ca2+ transient, cAMP production and pacemaker frequency of rabbit sinoatrial node cells

We investigated the contribution of the intracellular calcium (Cai2+) transient to acetylcholine (ACh)-mediated reduction of pacemaker frequency and cAMP content in rabbit sinoatrial nodal (SAN) cells. Action potentials (whole cell perforated patch clamp) and Cai2+ transients (Indo-1 fluorescence) were recorded from single isolated rabbit SAN cells, whereas intracellular cAMP content was measured in SAN cell suspensions using a cAMP assay (LANCE®). Our data show that the Cai2+ transient, like the hyperpolarization-activated “funny current” (If) and the ACh-sensitive potassium current (IK,ACh), is an important determinant of ACh-mediated pacemaker slowing. When If and IK,ACh were both inhibited, by cesium (2 mM) and tertiapin (100 nM), respectively, 1 μM ACh was still able to reduce pacemaker frequency by 72%. In these If and IK,ACh-inhibited SAN cells, good correlations were found between the ACh-mediated change in interbeat interval and the ACh-mediated change in Cai2+ transient decay (r2 = 0.98) and slow diastolic Cai2+ rise (r2 = 0.73). Inhibition of the Cai2+ transient by ryanodine (3 μM) or BAPTA-AM (5 μM) facilitated ACh-mediated pacemaker slowing. Furthermore, ACh depressed the Cai2+ transient and reduced the sarcoplasmic reticulum (SR) Ca2+ content, all in a concentration-dependent fashion. At 1 μM ACh, the spontaneous activity and Cai2+ transient were abolished, but completely recovered when cAMP production was stimulated by forskolin (10 μM) and IK,ACh was inhibited by tertiapin (100 nM). Also, inhibition of the Cai2+ transient by ryanodine (3 μM) or BAPTA-AM (25 μM) exaggerated the ACh-mediated inhibition of cAMP content, indicating that Cai2+ affects cAMP production in SAN cells. In conclusion, muscarinic receptor stimulation inhibits the Cai2+ transient via a cAMP-dependent signaling pathway. Inhibition of the Cai2+ transient contributes to pacemaker slowing and inhibits Cai2+-stimulated cAMP production. Thus, we provide functional evidence for the contribution of the Cai2+ transient to ACh-induced inhibition of pacemaker activity and cAMP content in rabbit SAN cells