scholarly journals Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure

Toxics ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 217
Author(s):  
Chung-Yao Hsu ◽  
Yao-Chung Chuang ◽  
Fang-Chia Chang ◽  
Hung-Yi Chuang ◽  
Terry Ting-Yu Chiou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lead Exposure ◽  
Clock Gene ◽  
Slow Wave Sleep ◽  
Clock Genes ◽  
Negative Impact ◽  
Dark Period ◽  
Clock Gene Expression ◽  
Sleep Homeostasis ◽  
Chronic Lead Exposure

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep–wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague–Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep–wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep–wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep–wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.

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.

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 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 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.

scholarly journals Influence of obesity, weight loss, and free fatty acids on skeletal muscle clock gene expression

2020 ◽  
Vol 318 (1) ◽  
pp. E1-E10 ◽  
Author(s):  
Laura Sardon Puig ◽  
Nicolas J. Pillon ◽  
Erik Näslund ◽  
Anna Krook ◽  
Juleen R. Zierath
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Expression Profiles ◽  
Normal Weight ◽  
Nonesterified Fatty Acid ◽  
Clock Gene Expression

The molecular circadian clock plays a role in metabolic homeostasis. We tested the hypothesis obesity and systemic factors associated with insulin resistance affect skeletal muscle clock gene expression. We determined clock gene expression in skeletal muscle of obese women ( n = 5) and men ( n = 18) before and 6 mo after Roux-en-Y gastric bypass (RYGB) surgery and normal-weight controls (women n = 6, men n = 8). Skeletal muscle clock gene expression was affected by obesity and weight loss. CRY1 mRNA ( P = 0.05) was increased and DBP mRNA ( P < 0.05) was decreased in obese vs. normal weight women and restored to control levels after RYGB-induced weight loss. CLOCK, CRY1, CRY2, and DBP mRNA ( P < 0.05) was decreased in obese men compared with normal weight men. Expression of all other clock genes was unaltered by obesity or weight loss in both cohorts. We correlated clock gene expression with clinical characteristics of the participants. Among the genes studied, DBP and PER3 expression was inversely correlated with plasma lipids in both cohorts. Circadian time-course studies revealed that core clock genes oscillate over time ( P < 0.05), with BMAL1, CIART, CRY2, DBP, PER1, and PER3 expression profiles altered by palmitate treatment. In conclusion, skeletal muscle clock gene expression and function is altered by obesity, coincident with changes in plasma lipid levels. Palmitate exposure disrupts clock gene expression in myotubes, indicating that dyslipidemia directly alters the circadian program. Strategies to reduce lipid overload and prevent elevations in nonesterified fatty acid and cholesterol levels may sustain circadian clock signals in skeletal muscle.

scholarly journals Multiple Effects of Melatonin on Rhythmic Clock Gene Expression in the Mammalian Pars Tuberalis

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 959-965 ◽  
Author(s):  
Jonathan D. Johnston ◽  
Benjamin B. Tournier ◽  
Hakan Andersson ◽  
Mireille Masson-Pévet ◽  
Gerald A. Lincoln ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Clock Genes ◽  
Day Length ◽  
Pars Tuberalis ◽  
Melatonin Secretion ◽  
Clock Gene Expression ◽  
Gene Profiles ◽  
Previous Phase

In mammals, changing day length modulates endocrine rhythms via nocturnal melatonin secretion. Studies of the pituitary pars tuberalis (PT) suggest that melatonin-regulated clock gene expression is critical to this process. Here, we considered whether clock gene rhythms continue in the PT in the absence of melatonin and whether the effects of melatonin on the expression of these genes are temporally gated. Soay sheep acclimated to long photoperiod (LP) were transferred to constant light for 24 h, suppressing endogenous melatonin secretion. Animals were infused with melatonin at 4-h intervals across the final 24 h, and killed 3 h after infusion. The expression of five clock genes (Per1, Per2, Cry1, Rev-erbα, and Bmal1) was measured by in situ hybridization. In sham-treated animals, PT expression of Per1, Per2, and Rev-erbα showed pronounced temporal variation despite the absence of melatonin, with peak times occurring earlier than predicted under LP. The time of peak Bmal1 expression remained LP-like, whereas Cry1 expression was continually low. Melatonin infusion induced Cry1 expression at all times and suppressed other genes, but only when they showed high expression in sham-treated animals. Hence, 3 h after melatonin treatment, clock gene profiles were driven to a similar state, irrespective of infusion time. In contrast to the PT, melatonin infusions had no clear effect on clock gene expression in the suprachiasmatic nuclei. Our results provide the first example of acute sensitivity of multiple clock genes to one endocrine stimulus and suggest that rising melatonin levels may reset circadian rhythms in the PT, independently of previous phase.

scholarly journals Depriving mice of sleep also deprives of food

2021 ◽  
Author(s):  
Nina Đukanović ◽  
Francesco La Spada ◽  
Yann Emmenegger ◽  
Guy Niederhäuser ◽  
Frédéric Preitner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Food Deprivation ◽  
Clock Gene ◽  
Clock Genes ◽  
Energy Deficit ◽  
Clock Gene Expression ◽  
Recovery Sleep ◽  
Tightly Coupled ◽  
Access To Food

Both sleep-wake behavior and circadian rhythms are tightly coupled to energy metabolism and food intake. Altered feeding times in mice are known to entrain clock-gene rhythms in brain and liver and sleep-deprived humans tend to eat more and gain weight. Previous observations in mice showing that sleep deprivation (SD) changes clock-gene expression might thus relate to altered food intake and not to the loss of sleep per se. Whether SD affects food intake in the mouse and how this might affect clock-gene expression is, however, unknown. We therefore quantified i) the cortical expression of the clock genes Per1, Per2, Dbp, and Cry1 in mice that had access to food or not during a 6h SD, and ii) food intake during baseline, SD, and recovery sleep. We found that food deprivation did not modify the SD-incurred clock-gene changes in the cortex. Moreover, we discovered that although food intake during SD did not differ from baseline, mice lost weight and increased food intake during subsequent recovery. We conclude that SD is associated with food deprivation and that the resulting energy deficit might contribute to the effects of SD that are commonly interpreted as a response to sleep loss.

scholarly journals The Circadian Oscillator of the Cerebellum: Triiodothyronine Regulates Clock Gene Expression in Granule Cells in vitro and in the Cerebellum of Neonatal Rats in vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Tenna Bering ◽  
Henrik Hertz ◽  
Martin Fredensborg Rath
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Granule Cells ◽  
Clock Genes ◽  
Circadian Oscillator ◽  
Neonatal Rats ◽  
Clock Gene Expression ◽  
Mixed Gender

The central circadian clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, but an SCN-dependent molecular circadian oscillator is present in the cerebellar cortex. Recent findings suggest that circadian release of corticosterone is capable of driving the circadian oscillator of the rat cerebellum. To determine if additional neuroendocrine signals act to shape cerebellar clock gene expression, we here tested the role of the thyroid hormone triiodothyronine (T3) in regulation of the cerebellar circadian oscillator. In cultured cerebellar granule cells from mixed-gender neonatal rats, T3 treatment affected transcript levels of the clock genes Per2, Arntl, Nr1d1, and Dbp, suggesting that T3 acts directly on granule cells to control the circadian oscillator. We then used two different in vivo protocols to test the role of T3 in adult female rats: Firstly, a single injection of T3 did not influence clock gene expression in the cerebellum. Secondly, we established a surgical rat model combining SCN lesion with a programmable micropump infusing circadian physiological levels of T3; however, rhythmic infusion of T3 did not reestablish differential clock gene expression between day and night in SCN lesioned rats. To test if the effects of T3 observed in vitro were related to the developmental stage, acute injections of T3 were performed in mixed-gender neonatal rats in vivo; this procedure significantly affected cerebellar expression of the clock genes Per1, Per2, Nr1d1, and Dbp. Developmental comparisons showed rhythmic expression of all clock genes analyzed in the cerebellum of adult rats only, whereas T3 responsiveness was limited to neonatal animals. Thus, T3 shapes cerebellar clock gene profiles in early postnatal stages, but it does not represent a systemic circadian regulatory mechanism linking the SCN to the cerebellum throughout life.

scholarly journals Comparison of expression patterns of six canonical clock genes of follicular phase and luteal phase in Small-tailed Han sheep

2021 ◽  
Vol 64 (2) ◽  
pp. 457-466
Author(s):  
Qi Han ◽  
Xiaoyun He ◽  
Ran Di ◽  
Mingxing Chu
Keyword(s):  
Gene Expression ◽  
Estrous Cycle ◽  
Luteal Phase ◽  
Clock Gene ◽  
Clock Genes ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Clock Gene Expression ◽  
The Relationship ◽  
The Brain

Abstract. The circadian rhythm is a biological rhythm that is closely related to the rhythmic expression of a series of clock genes. Results from several studies have indicated that clock genes are associated with the estrous cycle in female animals. Until now, the relationship between estrus cycle transition and clock gene expression in reproductive-axis-related tissues has remained unknown in Small-tailed Han (STH) sheep. This study was conducted to analyze the expression patterns of six canonical clock genes (Clock, BMAL1, Per1, Per2, Cry1, and Cry2) in the follicle phase and luteal phase of STH sheep. We found that all six genes were expressed in the brain, cerebellum, hypothalamus, pituitary, ovary, uterus, and oviduct in follicle and luteal phases. The results indicated that Clock expression was significantly higher in the cerebellum, hypothalamus, and uterus of the luteal phase than that of the follicle phase, whereas BMAL1 expression was significantly higher in the hypothalamus of the luteal phase than that of the follicle phase. Per1 expression was significantly higher in the brain, cerebellum, hypothalamus, and pituitary of the luteal phase than that of the follicle phase, and Per2 expression was significantly higher in the hypothalamus, pituitary, and uterus of the luteal phase than that of the follicle phase. Cry1 expression was significantly higher in the brain, cerebellum, and hypothalamus of the luteal phase than that of the follicle phase, whereas Cry2 expression was significantly higher in the pituitary of the luteal phase than that of the follicle phase. The clock gene expression in all tissues was different between follicle and luteal phases, but all clock gene mRNA levels were found to exhibit higher expression among seven tissues in the luteal phase. Our results suggest that estrous cycles may be associated with clock gene expression in the STH sheep. This is the first study to systematically analyze the expression patterns of clock genes of different estrous cycle in ewes, which could form a basis for further studies to develop the relationship between clock genes and the estrous cycle.

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