Circadian rhythm of ERG in Iguana iguana: role of the pineal

In green iguanas, the pineal controls the circadian rhythm of body temperature but not the rhythm of locomotor activity. As part of a program to investigate the characteristics of this multioscillator circadian system, the authors studied the circadian rhythms of the electroretinographic response (ERG) and asked whether the pineal gland is necessary for the expression of this rhythm. ERGs from a total of 24 anesthetized juvenile iguanas were recorded under four different conditions: (a) complete darkness (DD), (b) dim light-dark cycles (dLD), (c) constant dim light (dLL), and (d) pinealectomized in DD. Results demonstrate that the b-wave component of the ERG shows a very clear circadian rhythm in DD and that this rhythm persists in dLL and entrains to dLD cycles. The ERG response is maximally sensitive during the subjective day. Pinealectomy does not abolish the circadian rhythm in ERG, demonstrating that the oscillator responsible for the ERG rhythm is located elsewhere.     

Interactions between dopamine and melatonin organize circadian rhythmicity in the retina of the green iguana

Circadian physiology in the vertebrate retina is regulated by several neurotransmitters. In the lateral eyes of the green iguana the circadian rhythm of melatonin content peaks during the night while the rhythm of dopamine peaks during the day. In the present work, the authors explore the interaction of these 2 neurotransmitters during the circadian cycle. They depleted retinal dopamine with intravitreal injections of 6-hydroxydopamine (6-OHDA) and measured ocular melatonin content in vivo throughout 1 circadian cycle. The circadian rhythm of ocular melatonin not only persisted but increased 10-fold in amplitude. This increase was substantially reduced by the intraocular administration of dopamine. 6-OHDA-treated retinas, unlike those from untreated animals, did not express a circadian rhythm of melatonin synthesis in vitro. To deplete retinal melatonin, the authors pinealectomized iguanas and blocked retinal melatonin synthesis by depleting serotonin with intraocular injections of 5,6-dihydroxytryptamine. In animals so treated, they found that the circadian rhythm of retinal dopamine content was abolished, the levels of dopamine were lowered, and the levels of dopamine metabolites were greatly increased. The data suggest that in iguanas, the amplitude of the circadian rhythm of melatonin synthesis in the eye is suppressed by dopamine while the rhythm of dopamine depends, at least in part, on the presence of melatonin.     

Localization of melatonin receptor 1 in mouse retina and its role in the circadian regulation of the electroretinogram and dopamine levels

Melatonin modulates many important functions within the eye by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylate cyclase. In the mouse, Melatonin Receptors type 1 (MT(1)) mRNAs have been localized to photoreceptors, inner retinal neurons, and ganglion cells, thus suggesting that MT(1) receptors may play an important role in retinal physiology. Indeed, we have recently reported that absence of the MT(1) receptors has a dramatic effect on the regulation of the daily rhythm in visual processing, and on retinal cell viability during aging. We have also shown that removal of MT(1) receptors leads to a small (3-4 mmHg) increase in the level of the intraocular pressure during the night and to a significant loss (25-30%) in the number of cells within the retinal ganglion cell layer during aging. In the present study we investigated the cellular distribution in the C3H/f(+/+) mouse retina of MT(1) receptors using a newly developed MT(1) receptor antibody, and then we determined the role that MT(1) signaling plays in the circadian regulation of the mouse electroretinogram, and in the retinal dopaminergic system. Our data indicate that MT(1) receptor immunoreactivity is present in many retinal cell types, and in particular, on rod and cone photoreceptors and on intrinsically photosensitive ganglion cells (ipRGCs). MT(1) signaling is necessary for the circadian rhythm in the photopic ERG, but not for the circadian rhythm in the retinal dopaminergic system. Finally our data suggest that the circadian regulation of dopamine turnover does not drive the photopic ERG rhythm.     

The pineal complex and melatonin affect the expression of the daily rhythm of behavioral thermoregulation in the green iguana

Daily variation in the body temperature of the green iguana (Iguana iguana) was studied by telemetry in laboratory photo-thermal enclosures under a 12Light12Dark (LD) photoperiod. The lizards showed robust daily rhythms of thermoregulation maintaining their body temperatures (T_b) at higher levels during the day than during the night. Some animals maintained rhythmicity when kept in constant darkness. On lightdark cycles parietalectomy produced only a transient increase of median T_b in the first or second night following the operation. Pinealectomized lizards on the other hand maintained their body temperatures at significantly lower levels during the day and at significantly higher levels during the night than did sham-operated or intact lizards. This effect was apparently permanent, since one month after pinealectomy lizards still displayed the altered pattern. Plasma melatonin levels in intact animals were high during the night and low during the day and were unaffected by parietalectomy. Pinealectomized lizards showed low levels of plasma melatonin during both the day and the night. A daily intraperitoneal injection of melatonin in pinealectomized animals given a few minutes after the light to dark transition decreased the body temperatures selected by the lizards during the night and increased the body temperatures selected during the following day. Control injections of saline solution had no effect. The significance of these results is discussed in relation to the role of the pineal complex and melatonin in the mediation of thermoregulatory behavior.Abbreviations LD LightDark - T _b body temperature - PAR-X parietalectomy - PIN-X pinealectomy     

Circadian locomotor rhythms in the desert iguana

Summary Desert iguanas, Dipsosaurus dorsalis, displaying freerunning circadian locomotor rhythms in conditions of constant darkness and temperature received electrolytic lesions to the hypothalamus. The locomotor activity of those lizards (N = 9) which sustained 80% or more damage to the suprachiasmatic nucleus (SCN) became arrhythmic whereas all animals that sustained less than 35% damage to the SCN remained rhythmic, even though they sustained significant damage to nearby regions of the hypothalamus and preoptic area. These results suggest strongly that the SCN plays a role in the regulation of circadian rhythms in the desert iguana. Taken together with other evidence, they support the view that this structure is homologous to the mammalian SCN, which acts as a pacemaker in the circadian system.Abbreviations SCN suprachiasmatic nucleus - freerunning circadian period     

Circadian locomotor rhythms in the desert iguana I. The role of the eyes and the pineal

Summary The pineal and the eyes are known to be important components in the circadian system of some species of lizards; their effects may be mediated by the hormone melatonin. We examined the role played by these structures in the desert iguana (Dipsosaurus dorsalis). Surgical removal of the pineal had no effect on circadian locomotor rhythms, even though this procedure abolished the circadian rhythm of melatonin in the blood. Furthermore, when the isolated pineal of Dipsosaurus was studied in organ culture, it showed no circadian rhythm of melatonin secretion, as do pineals of some other lizard species, although it did produce large quantities of this hormone. Bilateral ocular enucleation had only small effects on the freerunning period of locomotor rhythms, without affecting melatonin levels in the blood. Behavioral circadian rhythms persisted in desert iguanas subjected to both enucleation and pinealectomy. These data suggest that neither the pineal nor the eyes are central components of the circadian pacemaking system in Dipsosaurus, nor is melatonin critically involved in maintaining its organization.Abbreviations CT circadian time - ZT zeitgeber time - LL constant light - LD light-dark cycle - DD constant darkness - freerunning circadian period     

Circadian rhythm gene expression and daily melatonin levels vary in athletes and sedentary males

The circadian rhythm is a 24-h cycle in which cells control metabolic and physiological processes throughout the day. In this study, we compared the expression patterns of major circadian rhythm-related genes: from blood of Bmal1, Ror-α, Cry1, Per2, Per1, and Nr1d1. In addition, changes in patterns of melatonin levels were observed in 16 subjects, eight males rugby players and eight males who did not exercise regularly. Blood was collected at 6:00, 10:00, 18:00, and 22:00. Bmal1, Ror-α, Cry1, Per2 (p < 0.001), Per1 (p < 0.01), and Nr1d1 (p < 0.05) genes related to circadian rhythm was higher in rugby players than in sedentary males. However, melatonin levels were higher in sedentary males than in rugby players (p < 0.05). These results indicate that long-term exercise in athletes can increase the expression of genes related to circadian rhythm and these may have an effect on daily melatonin levels as well.     

Circadian rhythm of melatonin in the brain of the face fly, Musca autumnalis De Geer

Melatonin was radioimmunoassayed in extracts from brains of Musca autumnalis De Geer, the face fly, obtained 4h apart during 24h in 3 series pools of over 2 dozen brains at each of 6 or 7 circadian times. A circadian rhythm in the data expressed as percent of mean was demonstrated by the population-mean cosinor method. Face flies thus offer themselves for studies of melatonin-mediated chronomodulation by feedsideward mechanisms.     

Circadian rhythmicity in dopamine content of mammalian retina: role of the photoreceptors

Dopamine, the predominant retinal catecholamine, is a neurotransmitter and neuromodulator known to regulate light-adaptive retinal processes. Because dopamine influences several rhythmic events in the retina it is also a candidate for a retinal circadian signal. Using high performance liquid chromatography (HPLC), we have tested whether dopamine and its breakdown products are rhythmic in Royal College of Surgeons (RCS) rats with normal and dystrophic retinas. In both normal and mutant animals entrained to a 12-h light/12-h dark cycle, we found robust daily rhythms of dopamine and its two major metabolites. To address circadian rhythmicity of dopamine content, rats were entrained to light/dark cycles and released into constant darkness, using the circadian rhythm of wheel-running activity as a marker of each individual's circadian phase. Circadian rhythms of dopamine and metabolite content persisted in both wild type and retinally degenerate animals held for two weeks in constant darkness. Our results demonstrate for the first time clear circadian rhythms of dopamine content and turnover in a free-running mammal, and suggest that rods and cones are not required for dopamine rhythmicity.     

Circadian rhythms in the electroretinogram of the cockroach

Circadian regulation of the amplitude of the electroretinogram (ERG) of the cockroach Leucophaea maderae was investigated. Two components of the ERG exhibited circadian rhythms in amplitude. Interestingly, the peak amplitudes for the two rhythms were approximately 12 hr out of phase. The dominant corneal negative potential (the "sustained component") exhibited maximum amplitude during the subjective night. A second corneal negative potential (the "off-transient") was at a maximum during the subjective day. Intensity-response curves of the sustained component were measured at both the peak and trough of the rhythm. The results showed that the circadian rhythm in amplitude reflected a sensitivity change equivalent to 0.2-0.6 log unit of intensity. An effort was also made to identify the anatomical locus of the pacemaking oscillator for the ERG rhythm in a series of lesion experiments. Neural isolation of the optic lobe from the midbrain by bisection of the optic lobe proximal to the distal edge of the lobula had no effect on the circadian rhythm of ERG amplitude. Bisection of the optic lobe distal to the lobula abolished the ERG amplitude rhythm. These results suggest that the pacemaker is located in the optic lobe near the lobula; that its motion continues in the absence of neural connections with the rest of the nervous system; and that its regulation of ERG amplitude depends on neural pathways in the optic lobe.     

Circadian rhythm leaf movement of Phaseolus vulgaris and the role of calcium ions

Legume plants, due to their distinctive botanical characteristics, such as leaf movements, physiological characteristics, such as nitrogen fixation, and their abilities to endure environmental stresses, have important roles in sustainable pastures development. Leaf movement of legume plants is turgor regulated and osmotically active fluxes of ions between extensor and flexor of pulvinus cause this movement. To determine the role of calcium ions in circadian leaf movements of Phaseolus vulgaris L., a radiotracer technique experiment using ⁴⁵Ca ions were employed. Measurements were taken during circadian leaf movements, and samples were taken from different parts of the leaflet. The ⁴⁵Ca β-particle activity reduced from leaflet base pulvinus to leaf tip. The pulvinus had the highest activity, while the leaf tip had the lowest. By increase of the ratio of ⁴⁵Ca β-particle activity within flexor to extensor (Fl/Ex) the midrib-petiole angle, as an indicator of leaf movement, increased linearly during circadian leaf movement (r = 0.86). The ⁴⁵Ca β-particle activity of Flex/Ext ratio reduced linearly (r = −0.88) toward midnight. In conclusion, it was found that calcium ions accumulation is opposite to the fluxes of osmatically active ions and water movement. Calcium ions accumulate at less negative water potential side of the pulivnus.Key words: pulvinus, extensor, flexor, leaf movement, rhythm, circadian, calcium, Phaseolus vulgaris, radioactive     

Circadian rhythm disruption: health consequences

Circadian rhythms control many facets of biology and their disruption can be associated with severe pathological conditions. In healthy individuals, disturbances to the sleep-wake cycle can be the root cause of many problems. In the present review, we explore the major factors contributing to circadian rhythm disruption, including sleep disorders, jet lag, and shift work. The consequences of these disruptions on central and peripheral clocks and the important areas of the body controlled by them involve immune function and metabolism, as well as alterations in cognitive abilities, thereby impairing social and occupational behavior. Further work exploring clock genes, light exposure, and cellular changes will be critical for identifying how these factors interact to affect health and behavior.     

昼夜节律系统与成人昼夜节律睡眠觉醒障碍

昼夜节律是存在于所有生命体中、接近24小时的内源性生物节律。昼夜节律与社会或环境节律的长期不同步,会引起睡眠、情绪等一系列变化。本文阐述了昼夜节律系统与睡眠之间的联系,重点介绍成人昼夜节律睡眠觉醒障碍疾病的临床研究成果,以期加强临床医生对该病的认识和诊治。     

Near-ultraviolet radiation suppresses melatonin synthesis in the chicken retina: a role of dopamine

Effects of near-ultraviolet radiation (UV-A; 325-390 nm, peak at 365 nm) on melatonin content and activity of serotonin N-acetyltransferase (AA-NAT; a key regulatory enzyme in melatonin biosynthesis) were examined in the retina of chickens. Acute exposure of dark-adapted animals to UV-A light produced a marked decline in melatonin content and AA-NAT activity of the retina. The magnitude of the observed changes was dependent upon duration of the light pulse and age of chickens, with 1-2-week old birds being more sensitive to UV-A action than 6-7-week old ones. The decrease in the nocturnal AA-NAT activity evoked by a 5-min UV-A pulse gradually deepened during the first 30 min after the return of chickens to constant darkness, then the enzyme activity began to rise, reaching nearly complete restoration within 2.5 hr. Systemic administration to chickens of alpha-methyl-p-tyrosine (an inhibitor of catecholamine synthesis; 0.3 g/kg) blocked the suppressive effect of UV-A light on retinal AA-NAT activity. Haloperidol, sulpiride (blockers of D2-family of dopamine (DA) receptors) and 2-chloro-11-(4-methylpiperazino)dibenz[b,f]oxepin (an antagonist of D4-DA receptors), given intraocularly (1-100 nmol/eye) prevented the UV-A light-evoked decrease in AA-NAT activity in the chicken retina in a dose-dependent manner, while raclopride (300 nmol/eye), an antagonist of D2/D3-DA receptors, was ineffective. In dark-adapted chickens exposure to UV-A light increased the DA content of the retina. It is concluded that UV-A radiation, similar to visible light, potently suppresses melatonin biosynthesis in the retina of chicken, with a D4-dopaminergic signal playing the role of an intermediate in this action.     

Circadian rhythm sleep disorders: An update

Sleep and Biological Rhythms - The primary symptom of circadian rhythm sleep disorders (CRSDs) is the inability to sleep during the desired sleep time. CRSDs are divided into two broad classes: (i)...     

Circadian rhythm in melatonin release as a mechanism to reinforce the temporal organization of the circadian system in crayfish

Melatonin (MEL) is a conserved molecule with respect to its synthesis pathway and functions. In crayfish, MEL content in eyestalks (Ey) increases at night under the photoperiod, and this indoleamine synchronizes the circadian rhythm of electroretinogram amplitude, which is expressed by retinas and controlled by the cerebroid ganglion (CG). The aim of this study was to determine whether MEL content in eyestalks and CG or circulating MEL in hemolymph (He) follows a circadian rhythm under a free-running condition; in addition, it was tested whether MEL might directly influence the spontaneous electrical activity of the CG. Crayfish were maintained under constant darkness and temperature, a condition suitable for studying the intrinsic properties of circadian systems. MEL was quantified in samples obtained from He, Ey, and CG by means of an enzyme-linked immunosorbent assay, and the effect of exogenous MEL on CG spontaneous activity was evaluated by electrophysiological recording. Variation of MEL content in He, Ey, and CG followed a circadian rhythm that peaked at the same circadian time (CT). In addition, a single dose of MEL injected into the crayfish at different CTs reduced the level of spontaneous electrical activity in the CG. Results suggest that the circadian increase in MEL content directly affects the CG, reducing its spontaneous electrical activity, and that MEL might act as a periodical signal to reinforce the organization of the circadian system in crayfish.     

Circadian regulation of retinomotor movements. I. Interaction of melatonin and dopamine in the control of cone length

In lower vertebrates, cone retinomotor movements occur in response to changes in lighting conditions and to an endogenous circadian clock. In the light, cone myoids contract, while in the dark, they elongate. In order to test the hypothesis that melatonin and dopamine may be involved in the regulation of cone movement, we have used an in vitro eyecup preparation from Xenopus laevis that sustains light- and dark-adaptive cone retinomotor movement. Melatonin mimics darkness by causing cone elongation. Dark- and melatonin-induced cone elongation are blocked by dopamine. Dopamine also stimulates cone contraction in dark-adapted eyecups. The effect of dopamine appears to be mediated specifically by a dopamine receptor, possibly of the D2 type. The dopamine agonist apomorphine and the putative D2 agonist LY171555 induced cone contraction. In contrast, the putative D1 agonist SKF38393-A and specific alpha 1-, alpha 2-, and beta-adrenergic receptor agonists were without effect. Furthermore, the dopamine antagonist spiroperidol not only blocked light-induced cone contraction, but also stimulated cone elongation in the light. These results suggest that dopamine is part of the light signal for cone contraction, and that its suppression is part of the dark signal for cone elongation. Melatonin may affect cone movement indirectly through its influence on the dopaminergic system.