Circadian rhythms: timing the sense of smell

It is well established that Drosophila olfaction is under circadian control, yet the mechanisms underlying this temporal regulation have remained elusive. The kinase GPRK2 has now been identified as a critical link between the circadian clock and olfactory responses.     

Circadian basis of seasonal timing in higher vertebrates

Abstract

The two dominant environmental oscillations shape biology and survival of species: the day–night cycle and the succession of the seasons in the year. Organisms have adapted to anticipate these variations by evolving internal circadian (ca.- about, diem- day) and circannual clocks. The former enables the organisms to regulate physiological functions on a daily basis, and the latter on the annual basis. In mammals, the suprachiasmatic nuclei (SCN) of the anterior hypothalamus contain master pacemaker and orchestrate peripheral clocks in synchrony with the daily 24 h light-dark cycle, while in birds circadian pacemake is an interacting system principally located in the retina, pineal and the hypothalamus. In this mini review, we discuss the role of circadian clocks in regulation of seasonal timing in higher vertebrates, with reference to birds and mammals.     

Circadian timing of injury-induced cell proliferation in zebrafish

In certain vertebrates such as the zebrafish, most tissues and organs including the heart and central nervous system possess the remarkable ability to regenerate following severe injury. Both spatial and temporal control of cell proliferation and differentiation is essential for the successful repair and re-growth of damaged tissues. Here, using the regenerating adult zebrafish caudal fin as a model, we have demonstrated an involvement of the circadian clock in timing cell proliferation following injury. Using a BrdU incorporation assay with a short labeling period, we reveal high amplitude daily rhythms in S-phase in the epidermal cell layer of the fin under normal conditions. Peak numbers of S-phase cells occur at the end of the light period while lowest levels are observed at the end of the dark period. Remarkably, immediately following amputation the basal level of epidermal cell proliferation increases significantly with kinetics, depending upon the time of day when the amputation is performed. In sharp contrast, we failed to detect circadian rhythms of S-phase in the highly proliferative mesenchymal cells of the blastema. Subsequently, during the entire period of outgrowth of the new fin, elevated, cycling levels of epidermal cell proliferation persist. Thus, our results point to a preferential role for the circadian clock in the timing of epidermal cell proliferation in response to injury.     

Circadian rhythms and the evolution of photoperiodic timing in insects

This review discusses possible evolutionary trends in insect photoperiodism, mainly from a chronobiological perspective. A crucial step was the forging of a link between the hormones regulating diapause and the systems of biological rhythms, circadian or circannual, which have independently evolved in eukaryotes to synchronize physiology and behaviour to the daily cycles of light and darkness. In many of these responses a central feature is that the circadian system resets to a constant phase at the beginning of the subjective night, and then ‘measures’ the duration of the next scotophase. In ‘external coincidence’, one version of such a clock, light now has a dual role. First, it serves to entrain the circadian system to the stream of pulses making up the light/dark cycle and, second, it regulates the nondiapause/diapause switch in development by illuminating/not illuminating a specific light sensitive phase falling at the end of the critical night length. Important work by A. D. Lees on the aphid Megoura viciae using so‐called ‘night interruption experiments' demonstrates that pulses falling early in the night lead to long‐day effects that are reversible by a subsequent dark period longer than the critical night length and also show maximal sensitivity in the blue–green range of the spectrum. Pulses falling in the latter half of the night, however, produce long‐day effects that are irreversible by a subsequent long‐night and show a spectral sensitivity extending into the red. With movement to higher latitudes, insects develop genetic clines in various parameters, including critical night length, the number of long‐night cycles needed for diapause induction, the strength of the response, and the ‘depth’ or intensity of the diapause thus induced. Evidence for these and other types of photoperiodic response suggests that they provided strong selective advantages for insect survival.     

Circadian telomerase activity and DNA synthesis for timing peptide administration

DNA synthesis and telomerase activity were assessed in nude mice transplanted with hepatic carcinoma. Hepatic cancer cells (SMMC-7721) were implanted into both flanks of each of 14 BALB/C mice synchronized in 12 h of light alternating with 12 h of darkness (LD12:12) for 4 weeks. At 7 timepoints, tumor samples were collected for measurement of cellular DNA content by flow cytometry and telomerase activity by PCR-ELISA assay. Cosinor analyses determine a 24-h rhythm for all variables, showing a similar timing for the DNA-synthesis phase and telomerase activity. These results provide a model for exploring optimal timing of chronotherapy with peptides, especially for treatment with telomerase inhibitors.     

Circadian range of entrainment in the semilunar eclosion rhythm of the marine insect clunio marinus

The semilunar eclosion of the intertidal chironomid Clunio is controlled by a semilunar timing of pupation in combination with a daily timing of emergence. This results in reproductive activities of a laboratory population every 15 days at a distinct time of day (in nature mostly in correlation with the afternoon low water time on days with spring tides). The entrainment of the timing processes has been tested under various periods of the daily light-dark cycle in order to check the circadian organization of the timing mechanisms as suggested for the perception of the semilunar zeitgeber situation (a distinct phase relationship between the 24 h light-dark cycle and the 12.4 h tidal cycle recurring after every 15th light-dark cycle, named semimonthly zeitgeber cycle) as well as for the daily zeitgeber (the 24 h light-dark cycle). With respect to the semilunar timing, a strong entrainment was only possible in semimonthly zeitgeber cycles with light-dark cycle periods close to the 24-h day (light-dark cycles of 10:10 to 14:14). This limited circadian range of entrainment of an endogenous circasemilunar long-term rhythm (syn. oscillator) conforms with the hypothesis for a circadian clock component as an intrinsic part of the semilunar zeitgeber perception.The range of entrainment for the daily timing was obviously wider which may be discussed either in relation to a multioscillatory circadian organization of the midges or in relation to different coupling characteristics of one circadian oscillator during semilunar and daily timing.     

Neuropsychological mechanisms of interval timing behavior

Interval timing in the seconds-to-minutes range is believed to underlie a variety of complex behaviors in humans and other animals. One of the more interesting problems in interval timing is trying to understand how the brain times events lasting for minutes with millisecond-based neural processes. Timing models proposing the use of coincidence-detection mechanisms (e.g., the detection of simultaneous activity across multiple neural inputs) appear to be the most compatible with known neural mechanisms. From an evolutionary perspective, coincidence detection of neuronal activity may be a fundamental mechanism of timing that is expressed across a wide variety of species. BioEssays 22:94-103, 2000.     

Circadian timing mechanism in the prokaryotic clock system of cyanobacteria

Cyanobacteria are the simplest organisms known to exhibit circadian rhythms and have provided experimental model systems for the dissection of basic properties of circadian organization at the molecular, physiological, and ecological levels. This review focuses on the molecular and genetic mechanisms of circadian rhythm generation in cyanobacteria. Recent analyses have revealed the existence of multiple feedback processes in the prokaryotic circadian system and have led to a novel molecular oscillator model. Here, the authors summarize current understanding of, and open questions about, the cyanobacterial oscillator.     

Circadian rhythms of blood components in dementia senilis

In eleven patients with dementia senilis circadian rhythms of hematocrit, hemoglobin, erythrocytes, leukocytes, serum iron and transferrin were studied by means of the cosinor method. An evident circadian rhythm was observed for all blood components, except leukocytes. There were no significant differences between patients with dementia senilis and healthy aged persons as far as hematocrit, hemoglobin, erythrocytes, and leukocytes are concerned. Acrophase for serum iron and transferrin occurs a little earlier and mesor is lower than in healthy aged persons.     

Distinct timing mechanisms produce discrete and continuous movements

The differentiation of discrete and continuous movement is one of the pillars of motor behavior classification. Discrete movements have a definite beginning and end, whereas continuous movements do not have such discriminable end points. In the past decade there has been vigorous debate whether this classification implies different control processes. This debate up until the present has been empirically based. Here, we present an unambiguous non-empirical classification based on theorems in dynamical system theory that sets discrete and continuous movements apart. Through computational simulations of representative modes of each class and topological analysis of the flow in state space, we show that distinct control mechanisms underwrite discrete and fast rhythmic movements. In particular, we demonstrate that discrete movements require a time keeper while fast rhythmic movements do not. We validate our computational findings experimentally using a behavioral paradigm in which human participants performed finger flexion-extension movements at various movement paces and under different instructions. Our results demonstrate that the human motor system employs different timing control mechanisms (presumably via differential recruitment of neural subsystems) to accomplish varying behavioral functions such as speed constraints.     

Circadian clock gene expression in the coral Favia fragum over diel and lunar reproductive cycles

Natural light cycles synchronize behavioral and physiological cycles over varying time periods in both plants and animals. Many scleractinian corals exhibit diel cycles of polyp expansion and contraction entrained by diel sunlight patterns, and monthly cycles of spawning or planulation that correspond to lunar moonlight cycles. The molecular mechanisms for regulating such cycles are poorly understood. In this study, we identified four molecular clock genes (cry1, cry2, clock and cycle) in the scleractinian coral, Favia fragum, and investigated patterns of gene expression hypothesized to be involved in the corals' diel polyp behavior and lunar reproductive cycles. Using quantitative PCR, we measured fluctuations in expression of these clock genes over both diel and monthly spawning timeframes. Additionally, we assayed gene expression and polyp expansion-contraction behavior in experimental corals in normal light:dark (control) or constant dark treatments. Well-defined and reproducible diel patterns in cry1, cry2, and clock expression were observed in both field-collected and the experimental colonies maintained under control light:dark conditions, but no pattern was observed for cycle. Colonies in the control light:dark treatment also displayed diel rhythms of tentacle expansion and contraction. Experimental colonies in the constant dark treatment lost diel patterns in cry1, cry2, and clock expression and displayed a diminished and less synchronous pattern of tentacle expansion and contraction. We observed no pattern in cry1, cry2, clock, or cycle expression correlated with monthly spawning events suggesting these genes are not involved in the entrainment of reproductive cycles to lunar light cycles in F. fragum. Our results suggest a molecular clock mechanism, potentially similar to that in described in fruit flies, exists within F. fragum.     

Circadian rhythms in phonological and visuospatial storage components of working memory

Working memory is a basic cognitive process that temporarily maintains the information necessary for the performance of many complex tasks such as reading comprehension, learning and reasoning. Working memory includes two storage components: phonological and visuospatial, and a central executive control. The objective of this study was to identify possible circadian rhythms in phonological and visuospatial storage components of working memory using a constant routine protocol. Participants were eight female undergraduate students, aged 17.5±0.93, range = 16 - 19 years old. They were recorded in the laboratory in a constant routine protocol during 30 h. Rectal temperature was recorded every minute; subjective sleepiness and tiredness, as well as phonological and visuospatial working memory tasks, were assessed each hour. There were circadian variations in correct responses in phonological and visuospatial working memory tasks. Cross-correlation analysis showed a 1-h phase delay of the phonological storage component and a 3-h phase delay of the visuospatial storage component with respect to rectal temperature. This result may explain the changes in the performance of many complex tasks during the day.     

Circadian rhythms, oxidative stress, and antioxidative defense mechanisms

Endogenous circadian and exogenously driven daily rhythms of antioxidative enzyme activities and of low molecular weight antioxidants (LMWAs) are described in various phylogenetically distant organisms. Substantial amplitudes are detected in several cases, suggesting the significance of rhythmicity in avoiding excessive oxidative stress. Mammalian and/or avian glutathione peroxidase and, as a consequence, glutathione reductase activities follow the rhythm of melatonin. Another hint for an involvement of melatonin in the control of redox processes is seen in its high-affinity binding to cytosolic quinone reductase 2, previously believed to be a melatonin receptor. Although antioxidative protection by pharmacological doses of melatonin is repeatedly reported, explanations of these findings are still insufficient and their physiological and chronobiological relevance is not yet settled. Recent data indicate a role of melatonin in the avoidance of mitochondrial radical formation, a function which may prevail over direct scavenging. Rhythmic changes in oxidative damage of protein and lipid molecules are also reported. Enhanced oxidative protein modification accompanied by a marked increase in the circadian amplitude of this parameter is detected in the Drosophila mutant rosy, which is deficient in the LMWA urate. Preliminary evidence for the significance of circadian rhythmicity in diminishing oxidative stress comes from clock mutants. In Drosophila, moderately enhanced protein damage is described for the arrhythmic and melatonin null mutant per⁰, but even more elevated, periodic damage is found in the short-period mutant per^s, synchronized to LD 12:12. Remarkably large increases in oxidative protein damage, along with impairment of tissue integrity and—obviously insufficient—compensatory elevations in protective enzymes are observed in a particularly vulnerable organ, the Harderian gland, of another short-period mutant tau, in the Syrian hamster. Mice deficient in the per2 gene homolog are reported to be cancer-prone, a finding which might also relate to oxidative stress. In the dinoflagellate Lingulodinium polyedrum [Gonyaulax polyedra], various treatments that cause oxidative stress result in strong suppressions of melatonin and its metabolite 5-methoxytryptamine (5-MT) and to secondary effects on overt rhythmicity. The glow maximum, depending on the presence of elevated 5-MT at the end of subjective night, decreases in a dose-dependent manner already under moderate, non-lethal oxidative stress, but is restored by replenishing melatonin. Therefore, a general effect of oxidative stress may consist in declines of easily oxidizable signaling molecules such as melatonin, and this can have consequences on the circadian intraorganismal organization and expression of overt rhythms. Recent findings on a redox-sensitive input into the core oscillator via modulation of NPAS2/BMAL1 or CLK/BMAL1 heterodimer binding to DNA indicate a direct influence of cellular redox balance, including oxidative stress, on the circadian clock.     

Photochemical transformations of nucleic acid components in the presence of lunar soil

It has been demonstrated that lunar soil is an effective catalyzer of photolysis of thin-solid films of uracil and uridine. Uracil photolysis proceeds more intensively both in the presence of the lunar soil and in absence of the latter as compared to the photolysis of uridine. Together with photodestruction of uracil, the extension in the initial molecular structure takes place.