Entrainment of the master circadian clock by scheduled feeding

The master circadian clock, located in the mammalian suprachiasmatic nuclei (SCN), generates and coordinates circadian rhythmicity, i.e., internal organization of physiological and behavioral rhythms that cycle with a near 24-h period. Light is the most powerful synchronizer of the SCN. Although other nonphotic cues also have the potential to influence the circadian clock, their effects can be masked by photic cues. The purpose of this study was to investigate the ability of scheduled feeding to entrain the SCN in the absence of photic cues in four lines of house mouse ( Mus domesticus). Mice were initially housed in 12:12-h light/dark cycle with ad libitum access to food for 6 h during the light period followed by 4–6 mo of constant dark under the same feeding schedule. Wheel running behavior suggested and circadian PER2 protein expression profiles in the SCN confirmed entrainment of the master circadian clock to the onset of food availability in 100% (49/49) of the line 2 mice in contrast to only 4% (1/24) in line 3 mice. Mice from line 1 and line 4 showed intermediate levels of entrainment, 57% (8/14) and 39% (7/18), respectively. The predictability of entrainment vs. nonentrainment in line 2 and line 3 and the novel entrainment process provide a powerful tool with which to further elucidate mechanisms involved in entrainment of the SCN by scheduled feeding.

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General Anaesthesia Shifts the Murine Circadian Clock in a Time-Dependant Fashion

Clocks & Sleep ◽

10.3390/clockssleep3010006 ◽

2021 ◽

Vol 3 (1) ◽

pp. 87-97

Author(s):

Nicola M. Ludin ◽

Alma Orts-Sebastian ◽

James F. Cheeseman ◽

Janelle Chong ◽

Alan F. Merry ◽

...

Keyword(s):

Circadian Clock ◽

General Anaesthesia ◽

Wheel Running ◽

Phase Shifts ◽

Time Dependent ◽

Suprachiasmatic Nuclei ◽

Response Curves ◽

Inhalational Anaesthetic ◽

Locomotor Rhythms ◽

Time Dependent Analysis

Following general anaesthesia (GA), patients frequently experience sleep disruption and fatigue, which has been hypothesized to result at least in part by GA affecting the circadian clock. Here, we provide the first comprehensive time-dependent analysis of the effects of the commonly administered inhalational anaesthetic, isoflurane, on the murine circadian clock, by analysing its effects on (a) behavioural locomotor rhythms and (b) PER2::LUC expression in the suprachiasmatic nuclei (SCN) of the mouse brain. Behavioural phase shifts elicited by exposure of mice (n = 80) to six hours of GA (2% isoflurane) were determined by recording wheel-running rhythms in constant conditions (DD). Phase shifts in PER2::LUC expression were determined by recording bioluminescence in organotypic SCN slices (n = 38) prior to and following GA exposure (2% isoflurane). Full phase response curves for the effects of GA on behaviour and PER2::LUC rhythms were constructed, which show that the effects of GA are highly time-dependent. Shifts in SCN PER2 expression were much larger than those of behaviour (c. 0.7 h behaviour vs. 7.5 h PER2::LUC). We discuss the implications of this work for understanding how GA affects the clock, and how it may inform the development of chronotherapeutic strategies to reduce GA-induced phase-shifting in patients.

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Identification of novel pathways in pathogenesis of ketosis in dairy cows via iTRAQ/MS

Journal of Veterinary Research ◽

10.1515/jvetres-2016-0047 ◽

2016 ◽

Vol 60 (3) ◽

pp. 309-314 ◽

Cited By ~ 1

Author(s):

Shi Shu ◽

Chuchu Xu ◽

Cheng Xia ◽

Xinhuan Xiao ◽

Gang Wang ◽

...

Keyword(s):

Protein Expression ◽

Dairy Cows ◽

Expression Profiles ◽

The Novel ◽

Absolute Quantitation ◽

Subclinical Ketosis ◽

Isobaric Tag ◽

Production Increase ◽

Protein Expression Profiles ◽

New Evidence

AbstractIntroduction: To identify novel pathways involved in the pathogenesis of ketosis, an isobaric tag for relative and absolute quantitation/mass spectrometry was used to define differences in protein expression profiles between healthy dairy cows and those with clinical or subclinical ketosis.Material and Methods: To define the novel pathways of ketosis in cattle, the differences in protein expression were analysed by bioinformatics. Go Ontology and Pathway analysis were carried out for enrich the role and pathway of the different expression proteins between healthy dairy cows and those with clinical or subclinical ketosis.Results: Differences were identified in 19 proteins, 16 of which were relatively up-regulated while the remaining 3 were relatively down-regulated. Sorbitol dehydrogenase (SORD) and glyceraldehyde-3-phosphate dehydrogenase (G3PD) were up-regulated in cattle with ketosis. SORD and G3PD promoted glycolysis. These mechanisms lead to pyruvic acid production increase and ketone body accumulation.Conclusion: The novel pathways of glycolysis provided new evidence for the research of ketosis.

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What makes the brain tick?: The 24-hour clock in mammals

The Biochemist ◽

10.1042/bio02601019 ◽

2004 ◽

Vol 26 (1) ◽

pp. 19-21

Author(s):

Hugh Piggins

Keyword(s):

Circadian Clock ◽

Constant Temperature ◽

Ventral Surface ◽

Suprachiasmatic Nuclei ◽

The Us ◽

Small Structure ◽

The Brain ◽

Constant Dark

Almost 30 years ago, researchers in the US made the astonishing discovery that destroying a very small structure near the ventral surface of the brain (Figures 1A and 1B), the suprachiasmatic nuclei (SCN) of the hypothalamus, abolished daily (near 24 hour or circadian) behavioural rhythms in rodents1. In intact animals, such oscillations in behaviour and endocrine cycles are sustained when animals are kept under constant conditions (i.e. constant dark, constant temperature, etc.), demonstrating that they are endogenously generated. Remarkably, grafting foetal SCN tissue into the brains of SCN-lesioned arrhythmic adult animals rescues behavioural rhythms2, confirming that the SCN are indeed the sites of the brain's master circadian clock.

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Serotonergic afferents mediate activity-dependent entrainment of the mouse circadian clock

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.1.r265 ◽

1997 ◽

Vol 273 (1) ◽

pp. R265-R269 ◽

Cited By ~ 13

Author(s):

D. M. Edgar ◽

M. S. Reid ◽

W. C. Dement

Keyword(s):

Circadian Clock ◽

Wheel Running ◽

Activity Levels ◽

Suprachiasmatic Nuclei ◽

Vigorous Exercise ◽

Serotonin Content ◽

Running Activity ◽

Midbrain Raphe Nuclei ◽

Activity Dependent

The circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus receives serotonergic afferents from the midbrain raphe nuclei, but the functional role of this projection is unclear. In rodents, locomotor activity increases serotonin content in the SCN, and serotonergic agonists phase shift the circadian clock in a manner closely similar to voluntary bouts of vigorous exercise, suggesting that serotonergic afferents could be part of the activity-dependent entrainment mechanism. We investigated this possibility by selectively lesioning serotonin terminals within and adjacent to the SCN by local microinjection of 5,7-dihydroxytryptamine in mice pretreated with desipramine. This treatment decreased serotonin content 96 +/- 1% and 5-hydroxyindole-3-acetic acid content below levels of detection (nearly 100%) but did not decrease norepinephrine content or neuropeptide Y immunoreactivity in the SCN. These lesions did not alter subsequent running activity levels, yet rendered mice unable to synchronize to a regularly scheduled 2-h wheel running paradigm that entrained sham-lesioned controls. Serotonin afferents are thus necessary for activity-dependent entrainment in the mouse.

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Disrupted Neuronal Activity Rhythms in the Suprachiasmatic Nuclei of Vasoactive Intestinal Polypeptide-Deficient Mice

Journal of Neurophysiology ◽

10.1152/jn.01206.2006 ◽

2007 ◽

Vol 97 (3) ◽

pp. 2553-2558 ◽

Cited By ~ 77

Author(s):

T. M. Brown ◽

C. S. Colwell ◽

J. A. Waschek ◽

H. D. Piggins

Keyword(s):

Vasoactive Intestinal Polypeptide ◽

Wheel Running ◽

Brain Slices ◽

Suprachiasmatic Nuclei ◽

Wild Type ◽

Behavioral Rhythms ◽

Adult Mice ◽

Deficient Mice ◽

Intestinal Polypeptide

Vasoactive intestinal polypeptide (VIP), acting via the VPAC2 receptor, is a key signaling pathway in the suprachiasmatic nuclei (SCN), the master clock controlling daily rhythms in mammals. Most mice lacking functional VPAC2 receptors are unable to sustain behavioral rhythms and lack detectable SCN electrical rhythms in vitro. Adult mice that do not produce VIP (VIP/PHI−/−) exhibit less severe alterations in wheel-running rhythms, but the effects of this deficiency on the amplitude, phasing, or periodicity of their SCN cellular rhythms are unknown. To investigate this, we used suction electrodes to extracellularly record multiple- and single-unit electrical activity in SCN brain slices from mice with varying degrees of VIP deficiency, ranging from wild-type (VIP/PHI+/+) to heterozygous (VIP/PHI+/−) and VIP/PHI−/− animals. We found decreasing proportions of rhythmic cells in SCN slices from VIP/PHI+/+ (∼91%, n = 23) through VIP/PHI-/+ (∼71%, n = 28) to VIP/PHI−/− mice (62%; n = 37) and a parallel trend toward decreasing amplitude in the remaining rhythmic cells. SCN neurons from VIP/PHI−/− mice exhibited a broad range in the period and phasing of electrical rhythms, concordant with the known alterations in their behavioral rhythms. Further, treatment of VIP/PHI−/− slices with a VPAC2 receptor antagonist significantly reduced the proportion of oscillating neurons, suggesting that VPAC2 receptors still become activated in the SCN of these mice. The results establish that VIP is important for appropriate periodicity and phasing of SCN neuronal rhythms and suggest that residual VPAC2 receptor signaling promotes rhythmicity in adult VIP/PHI−/− mice.

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The characteristics of circRNA as competing endogenous RNA in pathogenesis of acute myeloid leukemia

BMC Cancer ◽

10.1186/s12885-021-08029-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Siyuan Zhang

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Expression Profiles ◽

Gene Expression Omnibus ◽

The Novel ◽

Competing Endogenous Rna ◽

Regulatory Modules ◽

Cerna Network ◽

Regulatory Module ◽

Acute Myeloid

Abstract Background As one of the novel molecules, circRNA has been identified closely involved in the pathogenesis of many diseases. However, the function of circRNA in acute myeloid leukemia (AML) still remains unknown. Methods In the current study, the RNA expression profiles were obtained from Gene Expression Omnibus (GEO) datasets. The differentially expressed RNAs were identified using R software and the competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed to identify the candidate circRNA-mediated aberrant signaling pathways. The hub genes were identified by MCODE and CytoHubba plugins of Cytoscape, and then a subnetwork regulatory module was established. Results A total of 27 circRNA-miRNA pairs and 208 miRNA-mRNA pairs, including 12 circRNAs, 24 miRNAs and 112 mRNAs were included in the ceRNA network. Subsequently, a subnetwork, including 4 circRNAs, 5 miRNAs and 6 mRNAs, was established based on related circRNA-miRNA-mRNA regulatory modules. Conclusions In summary, this work analyzes the characteristics of circRNA as competing endogenous RNA in AML pathogenesis, which would provide hints for developing novel prognostic, diagnostic and therapeutic strategy for AML.

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Transcriptomal dissection of soybean circadian rhythmicity in two geographically, phenotypically and genetically distinct cultivars

BMC Genomics ◽

10.1186/s12864-021-07869-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yanlei Yue ◽

Ze Jiang ◽

Enoch Sapey ◽

Tingting Wu ◽

Shi Sun ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Chromosome Structure ◽

Clock Genes ◽

Expression Profiles ◽

Circadian Rhythmicity ◽

Rna Seq ◽

Night Time ◽

Time Points ◽

Circadian Clock Genes

Abstract Background In soybean, some circadian clock genes have been identified as loci for maturity traits. However, the effects of these genes on soybean circadian rhythmicity and their impacts on maturity are unclear. Results We used two geographically, phenotypically and genetically distinct cultivars, conventional juvenile Zhonghuang 24 (with functional J/GmELF3a, a homolog of the circadian clock indispensable component EARLY FLOWERING 3) and long juvenile Huaxia 3 (with dysfunctional j/Gmelf3a) to dissect the soybean circadian clock with time-series transcriptomal RNA-Seq analysis of unifoliate leaves on a day scale. The results showed that several known circadian clock components, including RVE1, GI, LUX and TOC1, phase differently in soybean than in Arabidopsis, demonstrating that the soybean circadian clock is obviously different from the canonical model in Arabidopsis. In contrast to the observation that ELF3 dysfunction results in clock arrhythmia in Arabidopsis, the circadian clock is conserved in soybean regardless of the functional status of J/GmELF3a. Soybean exhibits a circadian rhythmicity in both gene expression and alternative splicing. Genes can be grouped into six clusters, C1-C6, with different expression profiles. Many more genes are grouped into the night clusters (C4-C6) than in the day cluster (C2), showing that night is essential for gene expression and regulation. Moreover, soybean chromosomes are activated with a circadian rhythmicity, indicating that high-order chromosome structure might impact circadian rhythmicity. Interestingly, night time points were clustered in one group, while day time points were separated into two groups, morning and afternoon, demonstrating that morning and afternoon are representative of different environments for soybean growth and development. However, no genes were consistently differentially expressed over different time-points, indicating that it is necessary to perform a circadian rhythmicity analysis to more thoroughly dissect the function of a gene. Moreover, the analysis of the circadian rhythmicity of the GmFT family showed that GmELF3a might phase- and amplitude-modulate the GmFT family to regulate the juvenility and maturity traits of soybean. Conclusions These results and the resultant RNA-seq data should be helpful in understanding the soybean circadian clock and elucidating the connection between the circadian clock and soybean maturity.

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