scholarly journals CLOCK Genes and Circadian Rhythmicity in Alzheimer Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
J. Thome ◽  
A. N. Coogan ◽  
A. G. Woods ◽  
C. C. Darie ◽  
F. Häßler
Keyword(s):  
Alzheimer Disease ◽  
Clock Gene ◽  
Clock Genes ◽  
Sleep Problems ◽  
Internal Clock ◽  
Circadian Rhythmicity ◽  
Clock Gene Expression ◽  
Endogenous Clock ◽  
Exogenous Factors ◽  
The Impact

Disturbed circadian rhythms with sleep problems and disrupted diurnal activity are often seen in patients suffering from Alzheimer disease (AD). Both endogenous CLOCK genes and external Zeitgeber are responsible for the maintenance of circadian rhythmicity in humans. Therefore, modifications of the internal CLOCK system and its interactions with exogenous factors might constitute the neurobiological basis for clinically observed disruptions in rhythmicity, which often have grave consequences for the quality of life of patients and their caregivers. Presently, more and more data are emerging demonstrating how alterations of the CLOCK gene system might contribute to the pathophysiology of AD and other forms of dementia. At the same time, the impact of neuropsychiatric medication on CLOCK gene expression is under investigation.

scholarly journals Shift Work, Jet Lag, and Female Reproduction

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Megan M. Mahoney
Keyword(s):  
Gene Expression ◽  
Shift Work ◽  
Clock Gene ◽  
Clock Genes ◽  
Reproductive Function ◽  
Jet Lag ◽  
Female Reproduction ◽  
Clock Gene Expression ◽  
Increased Risk ◽  
The Impact

Circadian rhythms and “clock gene” expression are involved in successful reproductive cycles, mating, and pregnancy. Alterations or disruptions of biological rhythms, as commonly occurs in shift work, jet lag, sleep deprivation, or clock gene knock out models, are linked to significant disruptions in reproductive function. These impairments include altered hormonal secretion patterns, reduced conception rates, increased miscarriage rates and an increased risk of breast cancer. Female health may be particularly susceptible to the impact of desynchronizing work schedules as perturbed hormonal rhythms can further influence the expression patterns of clock genes. Estrogen modifies clock gene expression in the uterus, ovaries, and suprachiasmatic nucleus, the site of the primary circadian clock mechanism. Further work investigating clock genes, light exposure, ovarian hormones, and reproductive function will be critical for indentifying how these factors interact to impact health and susceptibility to disease.

scholarly journals Clock gene expression is altered in veterans with sleep apnea

2019 ◽  
Vol 51 (3) ◽  
pp. 77-82 ◽  
Author(s):  
Muna T. Canales ◽  
Meaghan Holzworth ◽  
Shahab Bozorgmehri ◽  
Areef Ishani ◽  
I. David Weiner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sleep Apnea ◽  
Clock Gene ◽  
Clock Genes ◽  
Apnea Hypopnea Index ◽  
Blood Collection ◽  
Cross Sectional ◽  
Sleep Complaints ◽  
Clock Gene Expression ◽  
Metabolic Outcomes

Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m2 (SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.

Clock Gene Expression in the Submandibular Glands

2005 ◽  
Vol 84 (12) ◽  
pp. 1193-1197 ◽  
Author(s):  
M. Furukawa ◽  
T. Kawamoto ◽  
M. Noshiro ◽  
K.K. Honda ◽  
M. Sakai ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Clock Gene ◽  
Clock Genes ◽  
Expression Profiles ◽  
Mrna Levels ◽  
Peripheral Tissues ◽  
Submandibular Glands ◽  
Circadian Expression ◽  
Clock Gene Expression

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes—including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbα—showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1− /− background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.

scholarly journals Poor Sleep Quality Is Associated with Dawn Phenomenon and Impaired Circadian Clock Gene Expression in Subjects with Type 2 Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yuxin Huang ◽  
Haidong Wang ◽  
Yuan Li ◽  
Xiaoming Tao ◽  
Jiao Sun
Keyword(s):  
Sleep Quality ◽  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Poor Sleep ◽  
Poor Sleep Quality ◽  
Clock Gene Expression ◽  
Dawn Phenomenon ◽  
Circadian Clock Genes ◽  
Good Sleep

Aims. We investigated whether poor sleep quality is associated with both dawn phenomenon and impaired circadian clock gene expression in subjects with diabetes. Methods. 81 subjects with diabetes on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index. The magnitude of dawn phenomenon was quantified by its increment from nocturnal nadir to prebreakfast. Peripheral leucocytes were sampled from 81 subjects with diabetes and 28 normal controls at 09:00. Transcript levels of circadian clock genes (BMAL1, PER1, PER2, and PER3) were determined by real-time quantitative polymerase chain reaction. Results. The levels of HbA1c and fasting glucose and the magnitude of dawn phenomenon were significantly higher in the diabetes group with poor sleep quality than that with good sleep quality. Peripheral leucocytes from subjects with poor sleep quality expressed significantly lower transcript levels of BMAL1 and PER1 compared with those with good sleep quality. Poor sleep quality was significantly correlated with magnitude of dawn phenomenon. Multiple linear regression showed that sleep quality and PER1 were significantly independently correlated with dawn phenomenon. Conclusions. Dawn phenomenon is associated with sleep quality. Furthermore, mRNA expression of circadian clock genes is dampened in peripheral leucocytes of subjects with poor sleep quality.

scholarly journals Clock Gene Expression in Adult Primate Suprachiasmatic Nuclei and Adrenal: Is the Adrenal a Peripheral Clock Responsive to Melatonin?

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1454-1461 ◽  
Author(s):  
F. J. Valenzuela ◽  
C. Torres-Farfan ◽  
H. G. Richter ◽  
N. Mendez ◽  
C. Campino ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Clock Gene ◽  
Clock Genes ◽  
Phase Relationship ◽  
Suprachiasmatic Nuclei ◽  
Rhythmic Expression ◽  
Peripheral Oscillators ◽  
Clock Gene Expression ◽  
Timing System ◽  
Circadian Timing System

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.

scholarly journals P144 Clock gene expression levels inversely correlate with disease activity in ulcerative colitis and Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S228-S228
Author(s):  
Y Weintraub ◽  
S Cohen ◽  
N Chapnik ◽  
A Anafy ◽  
A Yerushalmy-Feler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Disease Activity ◽  
Clock Gene ◽  
Clock Genes ◽  
Clinical Status ◽  
Expression Levels ◽  
Clock Gene Expression ◽  
Gene Expression Levels

Abstract Background Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augment inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White Blood Cells (WBC). This reduction correlated with disease activity. Our aim in this study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC). Methods 17 patients with CD and 13 with UC, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and fecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (&lt;5 mg/l vs. &gt;5 mg/l) and Fcal levels (&lt; 250 μg/mg vs. &gt;250 μg/mg) in CD (21 samples) and UC (20 samples). Results In UC, BMAL (p&lt;0.008), CLOCK (p&lt;0.02), CRY1 (p&lt;0.002), CRY2 (p&lt;0.0009), PER1 (p&lt;0.003) and PER2 (p&lt;0.003) showed decreased expression when Fcal levels were &gt; 250 μg/mg. When compared with the clinical status and CRP levels, only BMAL1 showed reduced expression (p&lt;0.003 and p&lt;0.001, respectively). In CD, clinical status correlated with clock gene expression: CLOCK (p&lt;0.035), PER1 (p&lt;0.001) and CRY1 (p&lt;0.028) were reduced in active disease. CRP and Fcal did not correlate with clock gene expression. Conclusion Altered levels of certain clock genes were demonstrated in young CD and UC patients in exacerbation vs. remission. In UC, Fcal levels inversely correlated with all major circadian genes and partially with clinical status and CRP levels. In CD patients clock gene expression inversely correlated with clinical status.

scholarly journals Differential Expression of Circadian Clock Genes in the Bovine Neuroendocrine Adrenal System

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A66-A67
Author(s):  
Audrey L Earnhardt ◽  
David G Riley ◽  
Noushin Ghaffari ◽  
Penny K Riggs ◽  
Charles R Long ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Clock Gene ◽  
Target Genes ◽  
Clock Genes ◽  
Expression Profiles ◽  
Primary Objective ◽  
Clock Gene Expression ◽  
Adrenal System ◽  
Circadian Clock Genes

Abstract The primary objective of this investigation was to determine whether circadian clock genes were differentially expressed within or among bovine hypothalamic paraventricular nucleus (PVN), anterior pituitary gland (AP), adrenocortical (AC) and adrenomedullary (AM) tissues. The PVN, AP, AC, and AM were isolated from 5-yr-old Brahman cows (n = 8) harvested humanely at an abattoir between 0800-1100 h. Expression of target genes in each sample was evaluated via RNA-sequencing analyses. Gene counts were normalized using the trimmed mean of M values (TMM) method in the edgeR Package from Bioconductor, R. The normalized gene counts of genes important for circadian rhythm were statistically analyzed using the GLM Procedure of SAS. The genes analyzed were circadian locomotor output cycles protein kaput (CLOCK), cryptochrome circadian regulator 1 and 2 (CRY1 and CRY2), aryl hydrocarbon receptor nuclear translocator like (ARNTL), period circadian regulator 1 and 2 (PER1 and PER2), neuronal PAS domain protein 2 (NPAS2), and nuclear receptor subfamily 1 group D member 1 (NR1D1). Overall, relative expression profiles of clock genes differed (P &lt; 0.01) within each tissue with PER1 having greater expression in all tissues (P &lt; 0.01). Within the PVN expression of CLOCK, CRY1, ARNTL, and PER2 was less than that of CRY2, NPAS2, and NR1D1 (P &lt; 0.01). In the AP, with the exception of PER1, no other clock gene differed in degree of expression. In the AC, expression of CLOCK and NPAS2 was greater than CRY1, ARNTL, PER2, and NR1D1 (P &lt; 0.05), whereas CRY2 expression exceeded only CRY1 (P &lt; 0.05). Within the AM, CLOCK and CRY2 expression was greater than CRY1 and ARNTL (P &lt; 0.05). Overall, clock gene expression among tissues differed (P &lt; 0.01) for each individual clock gene. The AC and AM had similar clock gene expression, except expression of CRY2 and PER2 was greater in AM (P &lt; 0.05). The AC and AM had greater expression of CLOCK than the PVN and AP (P &lt; 0.01), with PVN having greater expression than AP (P &lt; 0.01). The AP had greater expression of NPAS2, followed by PVN, with the least expression in the AC and AM (P &lt; 0.01). Both PVN and AP had greater CRY1 and NR1D1 expression than AC or AM (P &lt; 0.01). The AP had greater PER1 expression than PVN, AC, and AM (P &lt; 0.01), whereas PVN, AC, and AM had greater ARNTL expression than AP (P &lt; 0.05). Both AP and AM had greater expression of PER2 than PVN or AC (P &lt; 0.01). The PVN had greater expression of CRY2 than the AP, AC, and AM (P &lt; 0.01). These results indicated that within each tissue the various clock genes were expressed in different quantities. Also, the clock genes were expressed differentially among the tissues of the bovine neuroendocrine adrenal system. Temporal relationships of these genes with the primary endocrine products of these tissues should be investigated to define the roles of peripheral clock genes in regulation of metabolism and health.

scholarly journals Rhythms during the polar night: evidence of clock-gene oscillations in the Arctic scallop Chlamys islandica

2020 ◽  
Vol 287 (1933) ◽  
pp. 20201001
Author(s):  
Mickael Perrigault ◽  
Hector Andrade ◽  
Laure Bellec ◽  
Carl Ballantine ◽  
Lionel Camus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Clock Genes ◽  
Biological Rhythms ◽  
The Arctic ◽  
Polar Night ◽  
Clock Gene Expression ◽  
Chlamys Islandica ◽  
Autumnal Equinox ◽  
Cyclic Variations

Arctic regions are highly impacted by climate change and are characterized by drastic seasonal changes in light intensity and duration with extended periods of permanent light or darkness. Organisms use cyclic variations in light to synchronize daily and seasonal biological rhythms to anticipate cyclic variations in the environment, to control phenology and to maintain fitness. In this study, we investigated the diel biological rhythms of the Arctic scallop, Chlamys islandica , during the autumnal equinox and polar night. Putative circadian clock genes and putative light perception genes were identified in the Arctic scallop. Clock gene expression oscillated in the three tissues studied (gills, muscle, mantle edge). The oscillation of some genes in some tissues shifted from daily to tidal periodicity between the equinox and polar night periods and was associated with valve behaviour. These results are the first evidence of the persistence of clock gene expression oscillations during the polar night and might suggest that functional clockwork could entrain rhythmic behaviours in polar environments.

Clock Genes Disruption in the Intensive Care Unit

2019 ◽  
Vol 35 (12) ◽  
pp. 1497-1504
Author(s):  
Elena Diaz ◽  
Irene Diaz ◽  
Cecilia del Busto ◽  
Dolores Escudero ◽  
Silvia Pérez
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Mrna Expression ◽  
Clock Gene ◽  
Clock Genes ◽  
Biological Clock ◽  
Icu Patients ◽  
Time Points ◽  
Icu Stay ◽  
The Impact

Background: Intensive care unit (ICU) environment disrupts the circadian rhythms due to environmental and other nonphotic synchronizers. The main purpose of this article is to establish whether critically patients have desynchronization at the molecular level after 1 week of stay in the ICU. Methods: The rhythm of Clock, Bmal1, Cry1, and Per2 genes in neuro-ICU patients (n = 11) on the first day after admission in the unit (1 day) and 1 week later (1 week) was studied, 4 time points throughout the day, at 6, 12, 18, and 24 hours. Human whole blood samples were obtained from neuro-ICU patients. The total RNA was isolated and each sample was reverse transcribed to complementary DNA and quantitative polymerase chain reaction (PCRq) was performed. The possible rhythm was studied using Fourier Series. Results: After 1 week, the clock gene rhythmicity completely disappeared. Messenger RNA (mRNA) expression for the 4 clock genes was shown rhythmicity at the first day after admission in the ICU. Circadian rhythmicity for none of them was observed but rather, ultradian rhythmicity was found. The expression of Clock, Bmal1, and Per2 mRNA after 1 week was similar in the 4-time point studies without significant fluctuation among the 4 time points analyzed. Discussion: Rhythmic mRNA expression is present at the first day after admission in the ICU. However, ICU stay during 1 week affects the molecular machinery of the biological clock generating chronodisruption. Circadian disruption is associated with the risk of several pathologies, thus, it seems to be clear that ICU stay in constant conditions could adversely affect patient evolution and probably, circadian resynchronization restoring clock gene expression could lead to a better clinical evolution of the patient. Conclusions: Clock genes disruption is observed in neuro-ICU patients. Light therapy as well as melatonin treatment could reduce the impact of ICU stay period in biological clock, thereby improving patients’ recovery.

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