scholarly journals Circadian Regulation of Vertebrate Cone Photoreceptor Function

2021 ◽  
Author(s):  
Jingjing Zang ◽  
Matthias Gesemann ◽  
Jennifer Keim ◽  
Marijana Samardzija ◽  
Christian Grimm ◽  
...  

Eukaryotes generally display a circadian rhythm as an adaption to the reoccurring day/night cycle. This is particularly true for visual physiology that is directly affected by changing light conditions. Here we investigate the influence of the circadian rhythm on the expression and function of visual transduction cascade regulators in diurnal zebrafish and nocturnal mice. We focused on regulators of shut-off kinetics such as recoverins, arrestins, opsin kinases, and GTPase-accelerating protein that have direct effects on temporal vision. Transcript as well as protein levels of most analyzed genes show a robust circadian rhythm dependent regulation, which correlates with changes in photoresponse kinetics. Electroretinography demonstrates that photoresponse recovery in zebrafish is delayed in the evening and accelerated in the morning. This physiological rhythmicity is mirrored in visual behaviors, such as optokinetic and optomotor responses. Functional rhythmicity persists in continuous darkness, it is reversed by an inverted light cycle and disrupted by constant light. This is in line with our finding that orthologous gene transcripts from diurnal zebrafish and nocturnal mice are often expressed in an anti-phasic daily rhythm.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jingjing Zang ◽  
Matthias Gesemann ◽  
Jennifer Keim ◽  
Marijana Samardzija ◽  
Christian Grimm ◽  
...  

Eukaryotes generally display a circadian rhythm as an adaption to the reoccurring day/night cycle. This is particularly true for visual physiology that is directly affected by changing light conditions. Here we investigate the influence of the circadian rhythm on the expression and function of visual transduction cascade regulators in diurnal zebrafish and nocturnal mice. We focused on regulators of shut-off kinetics such as Recoverins, Arrestins, Opsin kinases, and Regulator of G-protein signaling that have direct effects on temporal vision. Transcript as well as protein levels of most analyzed genes show a robust circadian rhythm-dependent regulation, which correlates with changes in photoresponse kinetics. Electroretinography demonstrates that photoresponse recovery in zebrafish is delayed in the evening and accelerated in the morning. Functional rhythmicity persists in continuous darkness, and it is reversed by an inverted light cycle and disrupted by constant light. This is in line with our finding that orthologous gene transcripts from diurnal zebrafish and nocturnal mice are often expressed in an anti-phasic daily rhythm.


Author(s):  
Michele Iovino ◽  
Tullio Messana ◽  
Giovanni De Pergola ◽  
Emanuela Iovino ◽  
Edoardo Guastamacchia ◽  
...  

Background and Objective: The sleep-wake cycle is characterized by a circadian rhythm involving neurotransmitters and neurohormones that are released from brainstem nuclei and hypothalamus. The aim of this review is to analyze the role played by central neural pathways, neurotransmitters and neurohormones in the regulation of vigilance states.Method:We analyzed the literature identifying relevant articles dealing with central neural pathways, neurotransmitters and neurohormones involved in the control of wakefulness and sleep.Results:The reticular activating system is the key center in the control of the states of wakefulness and sleep via alertness and hypnogenic centers. Neurotransmitters and neurohormones interplay during the dark-light cycle in order to maintain a normal plasmatic concentration of ions, proteins and peripheral hormones, and behavioral state control.Conclusion:An updated description of pathways, neurotransmitters and neurohormones involved in the regulation of vigilance states has been depicted.


ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.


2021 ◽  
Vol 7 (7) ◽  
pp. 538
Author(s):  
Rebecca Creamer ◽  
Deana Baucom Hille ◽  
Marwa Neyaz ◽  
Tesneem Nusayr ◽  
Christopher L. Schardl ◽  
...  

The legume Oxytropis sericea hosts a fungal endophyte, Alternaria oxytropis, which produces secondary metabolites (SM), including the toxin swainsonine. Polyketide synthase (PKS) and non-ribosomal peptide synthase (NRPS) enzymes are associated with biosynthesis of fungal SM. To better understand the origins of the SM, an unannotated genome of A. oxytropis was assessed for protein sequences similar to known PKS and NRPS enzymes of fungi. Contigs exhibiting identity with known genes were analyzed at nucleotide and protein levels using available databases. Software were used to identify PKS and NRPS domains and predict identity and function. Confirmation of sequence for selected gene sequences was accomplished using PCR. Thirteen PKS, 5 NRPS, and 4 PKS-NRPS hybrids were identified and characterized with functions including swainsonine and melanin biosynthesis. Phylogenetic relationships among closest amino acid matches with Alternaria spp. were identified for seven highly conserved PKS and NRPS, including melanin synthesis. Three PKS and NRPS were most closely related to other fungi within the Pleosporaceae family, while five PKS and PKS-NRPS were closely related to fungi in the Pleosporales order. However, seven PKS and PKS-NRPS showed no identity with fungi in the Pleosporales or the class Dothideomycetes, suggesting a different evolutionary origin for those genes.


2013 ◽  
Vol 451 (3) ◽  
pp. 453-461 ◽  
Author(s):  
Claudia C. S. Chini ◽  
Carlos Escande ◽  
Veronica Nin ◽  
Eduardo N. Chini

The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates circadian rhythm and metabolism. Rev-erbα controls circadian oscillations of several clock genes and Rev-erbα protein degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation. Elucidating the mechanisms that regulate Rev-erbα stability is essential for our understanding of these processes. In the present paper, we report that the protein DBC1 (Deleted in Breast Cancer 1) is a novel regulator of Rev-erbα. Rev-erbα and DBC1 interact in cells and in vivo, and DBC1 modulates the Rev-erbα repressor function. Depletion of DBC1 by siRNA (small interfering RNA) in cells or in DBC1-KO (knockout) mice produced a marked decrease in Rev-erbα protein levels, but not in mRNA levels. In contrast, DBC1 overexpression significantly enhanced Rev-erbα protein stability by preventing its ubiquitination and degradation. The regulation of Rev-erbα protein levels and function by DBC1 depends on both the N-terminal and C-terminal domains of DBC1. More importantly, in cells depleted of DBC1, there was a dramatic decrease in circadian oscillations of both Rev-erbα and BMAL1. In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbα and proposes that Rev-erbα could be involved in mediating some of the physiological effects of DBC1.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Maura Turriani ◽  
Nicola Bernabò ◽  
Barbara Barboni ◽  
Gianluca Todisco ◽  
Luigi Montini ◽  
...  

Serinus canariais a widespread domestic ornamental songbird, whose limited knowledge of biology make compelling studies aimed to monitor stress. Here, a commercial enzyme immunoassay was adopted to measure immunoreactive corticosterone (CORT) in singleSerinus canariadropping sample, to monitor the daily fecal excretion of CORT in birds bred singly or in-group and to detect the effect promoted by aviary or small transport cage restraint. A robust daily rhythm of CORT was recorded in animals held on short-day light cycle, independent of bred conditions (single or group), which persisted when space availability was modified in single bred animal (transfer in aviary and transport cages). By contrast, a significant change in CORT excretion was recorded when group bred animals are restrained in a smaller cage. The daily rhythm in CORT excretion in response to manipulation showed the greatest response at the beginning of the light period, followed by the absence of the peak usually recorded at the end of the dark phase. These data indicated that EIA could be used as a reliable noninvasive approach to monitor the stress induced by restraint conditions inSerinus canaria.


2017 ◽  
Vol 28 (22) ◽  
pp. 3095-3111 ◽  
Author(s):  
Courtney A. Copeland ◽  
Bing Han ◽  
Ajit Tiwari ◽  
Eric D. Austin ◽  
James E. Loyd ◽  
...  

Caveolin-1 (CAV1) is an essential component of caveolae and is implicated in numerous physiological processes. Recent studies have identified heterozygous mutations in the CAV1 gene in patients with pulmonary arterial hypertension (PAH), but the mechanisms by which these mutations impact caveolae assembly and contribute to disease remain unclear. To address this question, we examined the consequences of a familial PAH-associated frameshift mutation in CAV1, P158PfsX22, on caveolae assembly and function. We show that C-terminus of the CAV1 P158 protein contains a functional ER-retention signal that inhibits ER exit and caveolae formation and accelerates CAV1 turnover in Cav1–/– MEFs. Moreover, when coexpressed with wild-type (WT) CAV1 in Cav1–/– MEFs, CAV1-P158 functions as a dominant negative by partially disrupting WT CAV1 trafficking. In patient skin fibroblasts, CAV1 and caveolar accessory protein levels are reduced, fewer caveolae are observed, and CAV1 complexes exhibit biochemical abnormalities. Patient fibroblasts also exhibit decreased resistance to a hypo-osmotic challenge, suggesting the function of caveolae as membrane reservoir is compromised. We conclude that the P158PfsX22 frameshift introduces a gain of function that gives rise to a dominant negative form of CAV1, defining a new mechanism by which disease-associated mutations in CAV1 impair caveolae assembly.


2021 ◽  
Author(s):  
Bin Qiu ◽  
Zhaohui Zhong ◽  
Shawn Righter ◽  
Yuxue Xu ◽  
Jun Wang ◽  
...  

Abstract FK506-binding protein 51 (encoded by Fkpb51) has been associated with stress-related mental illness. To identify its function, we studied the morphological consequences of Fkbp51 deletion. Artificial Intelligence-assist morphological analysis identified that Fkbp51 knock-out (KO) mice possess more elongated CA and DG but shorter in height in coronal section when compared to WT. Primary cultured Fkbp51 KO hippocampal neurons were shown to exhibit larger dendritic outgrowth than wild-type (WT) controls, pharmacological manipulation experiments suggest that this may occur through regulation of microtubule-associated protein. Both in vitro primary culture and in vivo labeling support that FKBP51 regulates microtubule-associated protein expression. Furthermore, in the absence of differences in mRNA expression, Fkbp51 KO hippocampus exhibited decreases in βIII-tubulin, MAP2, and Tau protein levels, but a greater than 2.5-fold increase in Parkin protein. Overexpression and knock-down FKBP51 demonstrated that FKBP51 negatively regulates Parkin in a dose-dependent and ubiquitin-mediated manner. These results indicate a potential novel post-translational regulatory of Parkin by FKBP51 and significance of their interaction on disease onset.


1977 ◽  
Vol 66 (1) ◽  
pp. 47-64
Author(s):  
P. G. Sokolove ◽  
C. M. Beiswanger ◽  
D. J. Prior ◽  
A. Gelperin

The locomotor activity of the garden slug Limax maximus was examined for components of circadian rhythmicity. Behavioural (running wheel) studies clearly demonstrated that the activity satisfies the principal criteria of circadian rhythmicity. In constant darkness at a constant temperature, the locomotor activity freeran with a period of about 24 h (range 23-6-24-6 h). The rhythm was also expressed in constant light with a period for individual slugs that tended to be shorter in LL than in DD. The period of the rhythm was temperature compensated (11–5-21-5 degrees C) with a Q10 approximately equal to 1–00. The locomotor rhythm could be entrained to 24 h LD cycles such that the circadian activity peak occurred during the dark. The phase angle between the onset of activity and lights-off was not fixed, but was a function of the photoperiod of the entraining light cycle.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yanan Jiang ◽  
Xiuyun Shen ◽  
Moyondafoluwa Blessing Fasae ◽  
Fengnan Zhi ◽  
Lu Chai ◽  
...  

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.


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