scholarly journals The core clock genePer1phases molecular and electrical circadian rhythms in SCN neurons

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2297 ◽  
Author(s):  
Jeff R. Jones ◽  
Douglas G. McMahon
Keyword(s):  
Gene Expression ◽  
Firing Rate ◽  
Clock Gene ◽  
Biological Clock ◽  
Synaptic Activity ◽  
Spontaneous Firing ◽  
Transgenic Mouse Line ◽  
The Core ◽  
Clock Gene Expression ◽  
Spontaneous Firing Rate

The brain’s biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used aPer1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAAreceptor-mediated synaptic activity. Importantly, the concordant phasing of gene and neural rhythms is disrupted in the absence of the homologous clock genePer1, but persists in the absence of the core clock genePer2. These results suggest thatPer1plays a unique, non-redundant role in phasing gene expression and firing rate rhythms in SCN neurons to increase the robustness of cellular timekeeping.

scholarly journals Skipping Breakfast for 6 Days Delayed the Circadian Rhythm of the Body Temperature without Altering Clock Gene Expression in Human Leukocytes

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2797 ◽  
Author(s):  
Hitomi Ogata ◽  
Masaki Horie ◽  
Momoko Kayaba ◽  
Yoshiaki Tanaka ◽  
Akira Ando ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Temperature ◽  
Clock Gene ◽  
Core Body Temperature ◽  
The Core ◽  
Clock Gene Expression ◽  
Meal Timing ◽  
Dim Light ◽  
Core Body ◽  
Skipping Breakfast

Breakfast is often described as “the most important meal of the day” and human studies have revealed that post-prandial responses are dependent on meal timing, but little is known of the effects of meal timing per se on human circadian rhythms. We evaluated the effects of skipping breakfast for 6 days on core body temperature, dim light melatonin onset, heart rate variability, and clock gene expression in 10 healthy young men, with a repeated-measures design. Subjects were provided an isocaloric diet three times daily (3M) or two times daily (2M, i.e., breakfast skipping condition) over 6 days. Compared with the 3M condition, the diurnal rhythm of the core body temperature in the 2M condition was delayed by 42.0 ± 16.2 min (p = 0.038). On the other hand, dim light melatonin onset, heart rate variability, and clock gene expression were not affected in the 2M condition. Skipping breakfast for 6 days caused a phase delay in the core body temperature in healthy young men, even though the sleep–wake cycle remained unchanged. Chronic effects of skipping breakfast on circadian rhythms remain to be studied.

scholarly journals Simultaneous Monitoring of Behavior & Peripheral Clocks in Drosophila Reveals Unstructured Sleep in an Alzheimer's Model

2015 ◽  
Author(s):  
Eleonora Khabirova ◽  
Ko-Fan Chen ◽  
John S O'Neill ◽  
Damian C Crowther
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Biological Clock ◽  
Model Organisms ◽  
Clock Gene Expression ◽  
Biological Phenomena ◽  
Model Of Alzheimer’S Disease ◽  
Sleep Homeostasis ◽  
Regulatory Machinery ◽  
Activity Cycles

Sleep and circadian rhythms are ancient, related biological phenomena controlled by distinct neuronal circuits, whose appropriate regulation is critical for health. Whereas the regulatory machinery underlying sleep homeostasis is ill-defined, the biological clock mechanism is better understood: from cell-intrinsic feedback loops of ‘clock gene’ expression to circuits that facilitate rhythmic behavior. Age- and neurodegeneration related deterioration in sleep/wake timing was first described in humans decades ago, but has only recently been recapitulated in model organisms. In order to delineate the causal relationships between aging, sleep, neuronal function and the molecular clockwork, we have developed FLYGLOW, a broadly applicable bioluminescence-based system which allows rest/activity cycles, sleep consolidation and molecular clock gene expression to be quantified simultaneously in dozens of individual flies over many days/weeks. We show that FLYGLOW outperforms existing methods, and demonstrate the utility of the multiparameter correlational analyses within and between flies that it enables. We go on to show unambiguously that peripheral cellular rhythms can free-run independently of the central pacemakers that drive behavioural cycles. Finally, using a fly model of Alzheimer’s disease (AD) we observe a profound disorganization of sleep and activity cycles, that phenocopies the human disease.

scholarly journals The Tibetan medicineZuotaiinfluences clock gene expression in the liver of mice

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1632 ◽  
Author(s):  
Huan Li ◽  
Wen-Kai Li ◽  
Yuan-Fu Lu ◽  
Li-Xin Wei ◽  
Jie Liu
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Nuclear Receptor ◽  
Clock Gene ◽  
Target Genes ◽  
Oscillation Amplitude ◽  
Biological Clock ◽  
Tibetan Medicine ◽  
Pcr Analysis ◽  
Clock Gene Expression

Background.The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and “detoxification,” and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice.Materials and methods.Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose) daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression.Results.Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2), Brain and muscle Arnt-like protein-1 (Bmal1) at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1) and Period genes (Per1–3). For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp), decreased nuclear factor interleukin 3 (Nfil3) at 10:00, but had no effect on thyrotroph embryonic factor (Tef); Zuotai increased the expression of nuclear receptor Rev-Erbα (Nr1d1) at 18:00, but had little influence on the nuclear receptor Rev-Erbβ (Nr1d2) and RORα.Conclusion.The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai.

Pre- and Postsynaptic Inhibition Mediated by GABABReceptors in Cerebellar Inhibitory Interneurons

2002 ◽  
Vol 87 (1) ◽  
pp. 183-190 ◽  
Author(s):  
Puah Mann-Metzer ◽  
Yosef Yarom
Keyword(s):  
Synaptic Transmission ◽  
Firing Rate ◽  
Molecular Layer ◽  
Outward Current ◽  
Synaptic Activity ◽  
Lower Probability ◽  
Inhibitory Interneurons ◽  
Spontaneous Firing ◽  
Synaptic Potentials ◽  
Spontaneous Firing Rate

The inhibitory interneurons in the molecular layer of the cerebellar cortex form a complex network, interconnected by both chemical and electrotonic synapses. Previous work, using voltage optical imaging in an isolated cerebellum, has indicated that these interneurons also form presynaptic inhibitory interconnections. Here we examine the participation of GABABreceptors in the proposed presynaptic inhibition by recording from the molecular layer interneurons (MLI) in cerebellar slices. The GABAB agonist, baclofen, profoundly depressed synaptic transmission; a concentration of 10 μM decreased the frequency of spontaneous inhibitory synaptic potentials by 82 ± 15% and of miniature synaptic potentials by 75 ± 13%. In simultaneous recording from two synaptically interconnected MLIs, baclofen (10 μM) increased the failure rate of synaptic transmission by a factor of 3, confirming a presynaptic mechanism, most likely mediated by a decrease in calcium conductance. A postsynaptic effect of baclofen was also found; 10 μM decreased the spontaneous firing rate by 55 ± 19% even in the presence of synaptic blockers. One hundred micromolar baclofen induced an averaged hyperpolarization of 6 ± 2 mV or an averaged 7.8 ± 3 pA net outward current that can account for the decrease in firing rate. The outward current reflects a reduction in a tonic Ca2+ current, since it was abolished by blocking Ca2+ currents and remained unchanged in the presence of Ba2+. Application of the specific GABAB blocker, CGP 55845A (1 μM), not only reversed the effects of baclofen but also increased the spontaneous firing rate and synaptic activity when applied alone. Thus in slice preparations, GABABreceptors are tonically activated by endogenous GABA. The temporal role of GABAB receptors was tested using the paired-pulse paradigm. Recording from two synaptically interconnected MLIs showed a 3.5 times lower probability of release for the second stimulus. In the isolated cerebellar preparation, a robust depression of the second inhibitory response was observed. This depression was partially blocked by CGP 55845A (2 μM). We conclude that both the pre- and postsynaptic effects of baclofen are mediated by GABAB receptors that decrease Ca2+ currents. These can serve a modulatory role as well as participating in shaping the temporal interactions between consecutive inputs.

Generation of myometrium-specific Bmal1 knockout mice for parturition analysis

2012 ◽  
Vol 24 (5) ◽  
pp. 759 ◽  
Author(s):  
Christine K. Ratajczak ◽  
Minoru Asada ◽  
Gregg C. Allen ◽  
Douglas G. McMahon ◽  
Lisa M. Muglia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Time Window ◽  
Time Of Day ◽  
Conditional Knockout ◽  
Late Gestation ◽  
Mouse Line ◽  
Serum Progesterone ◽  
Transgenic Mouse Line ◽  
Clock Gene Expression

Human and rodent studies indicate a role for circadian rhythmicity and associated clock gene expression in supporting normal parturition. The importance of clock gene expression in tissues besides the suprachiasmatic nucleus is emerging. Here, a Bmal1 conditional knockout mouse line and a novel Cre transgenic mouse line were used to examine the role of myometrial Bmal1 in parturition. Ninety-two percent (22/24) of control females but only 64% (14/22) of females with disrupted myometrial Bmal1 completed parturition during the expected time window of 5 p.m. on Day 19 through to 9 a.m. on Day 19.5 of gestation. However, neither serum progesterone levels nor uterine transcript expression of the contractile-associated proteins Connexin43 and Oxytocin receptor differed between females with disrupted myometrial Bmal1 and controls during late gestation. The data indicate a role for myometrial Bmal1 in maintaining normal time of day of parturition.

scholarly journals Melatonin alleviated the immune response and improved the salivary gland function in primary Sjögren’s syndrome

2020 ◽  
Author(s):  
Yi Liu ◽  
Xiuhong Weng ◽  
Shaoling Yu ◽  
Yumei Ding ◽  
Bo Cheng
Keyword(s):  
Gene Expression ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Clock Gene ◽  
Clock Genes ◽  
Biological Clock ◽  
Lymphocyte Infiltration ◽  
Clock Gene Expression ◽  
Melatonin Administration ◽  
Gland Function

Abstract Background Excessive inflammatory reactions participate in primary Sjögren’s syndrome (pSS) progression. In addition, biological clock genes have been detected in the salivary glands, which indicates that clock genes regulate the growth and development of the salivary glands as well as the quality and quantity of saliva secretion. Melatonin is an amine hormone secreted by the pineal gland that has many physiological functions, such as regulating immunity and correcting disorder in the biological clock rhythm. The purpose of this study was to clarify the correlation between pSS and the biological clock rhythm and explore the possibility of applying melatonin to treat pSS. Methods Melatonin (10 mg/kg/d or 15 mg/kg/d) or vehicle was administered to NOD/Ltj mice by intraperitoneal injection for 4 weeks. Clock gene expression levels in labial gland biopsy specimens from pSS patients and submandibular gland specimens from mice were measured by Western blotting (WB) and RT-PCR. The salivary flow rate of mice was measured at 12, 14, and 16 weeks. The severity of lymphocyte infiltration in the salivary glands was analysed by haematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining were used to detect the expression levels of related inflammatory factors in mice. The percentages of Th17, Th2, and Treg cells were analysed by flow cytometry. Results There was a distinct expression profile for clock genes in pSS patients compared with controls. Continuous melatonin administration improved salivary gland function in NOD/Ltj mice, with decreased lymphocyte infiltration in the submandibular glands and reduced related inflammatory factor expression in the serum and salivary glands. Melatonin treatment skewed T cells towards the Treg and Th2 subsets while suppressing Th17 responses. Additionally, melatonin administration regulated clock gene expression in NOD/Ltj mice. Conclusion pSS pathogenesis and progression are correlated with abnormal circadian gene expression. Melatonin improves the hypofunction of the salivary glands and inhibits the inflammatory development of pSS in NOD/Ltj mice. This study provides a theoretical basis and potential approach for the clinical prevention and treatment of pSS.

Daily rhythm and regulation of clock gene expression in the rat pineal gland

2004 ◽  
Vol 120 (2) ◽  
pp. 164-172 ◽  
Author(s):  
V Simonneaux ◽  
V.-J Poirel ◽  
M.-L Garidou ◽  
D Nguyen ◽  
E Diaz-Rodriguez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pineal Gland ◽  
Clock Gene ◽  
Daily Rhythm ◽  
Clock Gene Expression ◽  
Rat Pineal Gland

A genetic CLOCK variant associated with cluster headache causing increased mRNA levels

Cephalalgia ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 496-502 ◽  
Author(s):  
Carmen Fourier ◽  
Caroline Ran ◽  
Margret Zinnegger ◽  
Anne-Sofie Johansson ◽  
Christina Sjöstrand ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Rhythm ◽  
Cluster Headache ◽  
Clock Gene ◽  
Control Sample ◽  
Mrna Levels ◽  
Nucleotide Polymorphisms ◽  
Primary Fibroblast ◽  
Clock Gene Expression ◽  
Diurnal Preference

Background Cluster headache is characterized by recurrent unilateral headache attacks of severe intensity. One of the main features in a majority of patients is a striking rhythmicity of attacks. The CLOCK ( Circadian Locomotor Output Cycles Kaput) gene encodes a transcription factor that serves as a basic driving force for circadian rhythm in humans and is therefore particularly interesting as a candidate gene for cluster headache. Methods We performed an association study on a large Swedish cluster headache case-control sample (449 patients and 677 controls) screening for three single nucleotide polymorphisms (SNPs) in the CLOCK gene implicated in diurnal preference (rs1801260) or sleep duration (rs11932595 and rs12649507), respectively. We further wanted to investigate the effect of identified associated SNPs on CLOCK gene expression. Results We found a significant association with rs12649507 and cluster headache ( p = 0.0069) and this data was strengthened when stratifying for reported diurnal rhythmicity of attacks ( p = 0.0009). We investigated the effect of rs12649507 on CLOCK gene expression in human primary fibroblast cultures and identified a significant increase in CLOCK mRNA expression ( p = 0.0232). Conclusions Our results strengthen the hypothesis of the involvement of circadian rhythm in cluster headache.

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