scholarly journals Altered Light Sensitivity of Circadian Clock in Shank3+/– Mouse

2021 ◽  
Vol 15 ◽  
Author(s):  
Javier Alamilla ◽  
Yazmín Ramiro-Cortés ◽  
Adriana Mejía-López ◽  
José-Luis Chavez ◽  
Dulce Olivia Rivera ◽  
...  

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan–McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3+/– mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3+/– mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light–dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3+/– mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing the N-methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3+/– animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3+/– mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons.

1993 ◽  
Vol 265 (5) ◽  
pp. R1199-R1204 ◽  
Author(s):  
T. Hamada ◽  
S. Shibata ◽  
A. Tsuneyoshi ◽  
K. Tominaga ◽  
S. Watanabe

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.


1977 ◽  
Vol 70 (1) ◽  
pp. 183-194
Author(s):  
JACK A. BENSON ◽  
JON W. JACKLET

1. The circadian rhythm of CAP frequency recorded from the optic nerve of isolated eyes at 15 °C was damped out by constant illumination (1100 lux) after several cycles of the rhythm. During illumination (LL) the rhythm was skewed with a rapid rising phase and slow falling phase, and the period was decreased by about 1 h. It is postulated that the circadian clock was stopped by LL at its lowest phase point, and that following cessation of LL, the rhythm was reinitiated from this phase point after a latency of 6-8 h. 2. For light pulses of 80 lux and 1100 lux, the photoresponse of the dark-adapted eye to 20 min light pulses applied beginning at 2 h intervals was not influenced by the circadian clock. At 5 lux there was a periodicity in the magnitude of the photoresponse, in phase with the circadian rhythm of spontaneous CAP production. 3. Small CAPs of non-circadian frequency were recorded together with normal CAPs in about 10% of records of output from isolated eyes. The cells producing the small CAPs had a different temperature sensitivity from those producing normal CAPs. The response of these cells to short light pulses consisted of a phasic burst of activity at light onset, followed by silence during the remainder of the short light pulse, and for 1 or 2 min following cessation of illumination. These small CAPs may be the activity either of H-type receptors or of secondary cells desynchronized from the major population. Note: Laboratory of Sensory Sciences, University of Hawaii at Manoa, 1993 East-West Road, Honolulu, Hawaii 96822, U.S.A.


2000 ◽  
Vol 278 (1) ◽  
pp. R201-R208 ◽  
Author(s):  
M. M. Canal-Corretger ◽  
T. Cambras ◽  
J. Vilaplana ◽  
A. Díez-Noguera

To examine the role of light in the maturation of the circadian pacemaker, twelve groups of rats were raised in different conditions of exposure to constant bright light (LL) during lactation: both duration and timing of LL were varied. We studied the motor activity rhythm of the rats after weaning, first under LL and then under constant darkness (DD). In DD, two light pulses [at circadian time 15 (CT15) and CT22] were applied to test the response of the pacemaker. Greater exposure to LL days during lactation increased the number of rhythmic animals and the amplitude of their motor activity rhythm in the LL stage and decreased the phase delay due to the light pulse at CT15. The timing of LL during lactation affected these variables too. Because the response of the adult to light depended on both the number and timing of LL days during lactation, the exposure to light at early stages may influence the development of the circadian system by modifying it structurally or functionally.


1995 ◽  
Vol 268 (2) ◽  
pp. R528-R535 ◽  
Author(s):  
K. Honma ◽  
S. Honma ◽  
K. Nakamura ◽  
M. Sasaki ◽  
T. Endo ◽  
...  

Reentrainment of human circadian rhythm to an 8-h advanced schedule of sleep and social contacts was assessed under two different conditions: with and without bright light (4,000-6,000 lx). Subjects spent 15 days without knowing the natural day-night alternation. On the fourth day, the social schedule was phase-advanced by 8 h. In one experiment, a bright light pulse of 3-h duration was given in every subjective morning, and in the other no light pulse was applied. Plasma melatonin and rectal temperature rhythms were measured. Seven of nine subjects showed an orthodromic phase shift, the rate of which was significantly larger with bright light pulses than without them. The maximum phase-advance shift by three consecutive light pulses was observed when the first pulse was applied approximately 4 h after the onset of melatonin rise. By contrast, the maximum phase shift of a similar extent was detected at 1 h after the onset of melatonin rise, when ordinary room light (300-500 lx) at the time corresponding to bright light was regarded as a dim light pulse. It is concluded that bright light accelerates the reentrainment of human circadian rhythm, and bright light and social schedule have differential effects on the reentrainment.


2002 ◽  
Vol 205 (1) ◽  
pp. 37-44
Author(s):  
Piotr Bebas ◽  
Bronislaw Cymborowski ◽  
Jadwiga M. Giebultowicz

SUMMARY Recent studies have demonstrated that the peripheral tissues of vertebrates and invertebrates contain circadian clocks; however, little is known about their functions and the rhythmic outputs that they generate. To understand clock-controlled rhythms at the cellular level, we investigated a circadian clock located in the reproductive system of a male moth (the cotton leaf worm Spodoptera littoralis) that is essential for the production of fertile spermatozoa. Previous work has demonstrated that spermatozoa are released from the testes in a daily rhythm and are periodically stored in the upper vas deferens (UVD). In this paper, we demonstrate a circadian rhythm in pH in the lumen of the UVD, with acidification occurring during accumulation of spermatozoa in the lumen. The daily rhythm in pH correlates with a rhythmic increase in the expression of a proton pump, the vacuolar H+-ATPase (V-ATPase), in the apical portion of the UVD epithelium. Rhythms in pH and V-ATPase persist in light/dark cycles and constant darkness, but are abolished in constant light, a condition that disrupts clock function and renders spermatozoa infertile. Treatment with colchicine impairs the migration of V-ATPase-positive vesicles to the apical cell membrane and abates the acidification of the UVD lumen. Bafilomycin, a selective inhibitor of V-ATPase activity, also prevents the decline in luminal pH. We conclude that the circadian clock generates a rhythm of luminal acidification by regulating the levels and subcellular distribution of V-ATPase in the UVD epithelium. Our data provide the first evidence for circadian control of V-ATPase, the fundamental enzyme that provides the driving force for numerous secondary transport processes. They also demonstrate how circadian rhythms displayed by individual cells contribute to the synchrony of physiological processes at the organ level.


2019 ◽  
Vol 34 (3) ◽  
pp. 272-282 ◽  
Author(s):  
Jia Zhao ◽  
Guy Robert Warman ◽  
Ralf Stanewsky ◽  
James Frederick Cheeseman

The importance of the circadian clock for the control of behavior and physiology is well established but how and when it develops is not fully understood. Here the initial expression pattern of the key clock gene period was recorded in Drosophila from embryos in vivo, using transgenic luciferase reporters. PERIOD expression in the presumptive central-clock dorsal neurons started to oscillate in the embryo in constant darkness. In behavioral experiments, a single 12-h light pulse given during the embryonic stage synchronized adult activity rhythms, implying the early development of entrainment mechanisms. These findings suggest that the central clock is functional already during embryogenesis. In contrast to central brain expression, PERIOD in the peripheral cells or their precursors increased during the embryonic stage and peaked during the pupal stage without showing circadian oscillations. Its rhythmic expression only initiated in the adult. We conclude that cyclic expression of PERIOD in the central-clock neurons starts in the embryo, presumably in the dorsal neurons or their precursors. It is not until shortly after eclosion when cyclic and synchronized expression of PERIOD in peripheral tissues commences throughout the animal.


2006 ◽  
Vol 36 (2) ◽  
pp. 337-347 ◽  
Author(s):  
L Appelbaum ◽  
D Vallone ◽  
A Anzulovich ◽  
L Ziv ◽  
M Tom ◽  
...  

Daily rhythms of melatonin production are controlled by changes in the activity of arylalkylamine-N-acetyltransferase (AANAT). Zebrafish possess two aanats, aanat1 and aanat2; the former is expressed only in the retina and the latter is expressed in both the retina and the pineal gland. Here, their differential expression and regulation were studied using transcript quantification and transient and stable in vivo and in vitro transfection assays. In the pineal gland, the aanat2 promoter exhibited circadian clock-controlled activity, as indicated by circadian rhythms of Enhanced green fluorescent protein (EGFP) mRNA in AANAT2:EGFP transgenic fish. In vivo transient expression analyses of the aanat2 promoter indicated that E-box and photoreceptor conserved elements (PCE) are required for expression in the pineal gland. In the retina, the expression of both genes was characterized by a robust circadian rhythm of their transcript levels. In constant darkness, the rhythmic expression of retinal aanat2 persisted while the aanat1 rhythm disappeared; indicating that the former is controlled by a circadian clock and the latter is also light driven. In the light-entrainable clock-containing PAC-2 zebrafish cell line, both stably transfected aanat1 and aanat2 promoters exhibited a clock-controlled circadian rhythm, characteristic for an E-box-driven expression. Transient co-transfection experiments in NIH-3T3 cells revealed that the two, E-box- and PCE-containing, promoters are driven by the synergistic action of BMAL/CLOCK and orthehodenticle homeobox 5. This study has revealed a shared mechanism for the regulation of two related genes, yet describes their differential phases and photic responses which may be driven by other gene-specific regulatory mechanisms and tissue-specific transcription factor profiles.


2020 ◽  
Vol 19 (2) ◽  
pp. 248-264 ◽  
Author(s):  
Ashish Sharma ◽  
Gautam Sethi ◽  
Murtaza M. Tambuwala ◽  
Alaa A. A. Aljabali ◽  
Dinesh Kumar Chellappan ◽  
...  

: All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.


2003 ◽  
Vol 284 (5) ◽  
pp. R1255-R1259 ◽  
Author(s):  
Setsuo Usui ◽  
Terue Okazaki ◽  
Yoshiko Honda

Ninety male Sprague-Dawley rats were exposed to 1:1-h light-dark (LD1:1) cycles for 50–90 days, and then they were released into constant darkness (DD). During LD1:1 cycles, behavioral rhythms were gradually disintegrated, and circadian rhythms of locomotor activity, drinking, and urine 6-sulfatoxymelatonin excretion were eventually abolished. After release into DD, 44 (49%) rats showed arrhythmic behavior for >10 days. Seven (8%) animals that remained arrhythmic for >50 days in DD were exposed to brief light pulses or 12:12-h light-dark cycles, and then they restored their circadian rhythms. These results indicate that the circadian clock was stopped, at least functionally, by LD1:1 cycles and was restarted by subsequent light stimulation.


2021 ◽  
Author(s):  
Aishwarya Segu ◽  
Nisha N Kannan

The circadian clock governs the timing of sleep-wake cycles as well as of other behavioural, physiological and metabolic processes. While the endogenous circadian clock mediates the timing of sleep, homeostatic mechanisms modulate the amount and depth of sleep. Evidence from previous studies showed that caffeine intake promotes wakefulness, whereas adult-stage specific caffeine treatment not only suppresses sleep but also delays the phase of circadian rhythm in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on circadian and homeostatic regulation of sleep. In the present study we examined the differential effect of acute and chronic caffeine treatment on sleep ontogeny as well as on circadian and homeostatic regulation of sleep in Drosophila. The results of our study showed that acute caffeine treatment reduces day and night sleep in mature flies through the homeostatic pathway whereas it reduced only the day sleep in young flies. Chronic caffeine treatment did not exert any significant effect on sleep in young flies. On the other hand, it delayed the timing of sleep in mature flies and in addition flies under higher caffeine concentration reduced the morning and evening anticipatory activity under 12 hour: 12 hour light: dark cycles. These flies also exhibited either a longer free running period or arrhythmicity under constant darkness. The results of our study showed that acute caffeine treatment suppresses sleep through the homeostatic pathway whereas prolonged caffeine treatment disrupts the circadian rhythm in mature flies.


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