scholarly journals Clock Gene Expression in the Human Pituitary Gland

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2046-2057 ◽  
Author(s):  
Florian Wunderer ◽  
Sina Kühne ◽  
Antje Jilg ◽  
Katrin Ackermann ◽  
Tamas Sebesteny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Clock Genes ◽  
Time Of Day ◽  
Adaptive Plasticity ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Hormone Synthesis ◽  
Clock Gene Expression ◽  
Pituitary Glands

Abstract Pituitary function relies on strictly timed, yet plastic mechanisms, particularly with respect to the daytime-dependent coordination of hormone synthesis and release. In other systems, clock genes and their protein products are well-described candidates to anticipate the daily demands in neuroendocrine coupling and to manage cellular adaptation on changing internal or external circumstances. To elucidate possible mechanisms of time management, a total of 52 human autoptic pituitary glands were allocated to the 4 time-of-day groups, night, dawn, day, and dusk, according to reported time of death. The observed daytime-dependent dynamics in ACTH content supports a postmortem conservation of the premortem condition, and thus, principally validates the investigation of autoptic pituitary glands. Pituitary extracts were investigated for expression of clock genes Per1, Cry1, Clock, and Bmal1 and corresponding protein products. Only the clock gene Per1 showed daytime-dependent differences in quantitative real-time PCR analyses, with decreased levels observed during dusk. Although the overall amount in clock gene protein products PER1, CRY1, and CLOCK did not fluctuate with time of day in human pituitary, an indication for a temporally parallel intracellular translocation of PER1 and CRY1 was detected by immunofluorescence. Presented data suggest that the observed clock gene expression in human pituitary cells does not provide evidence for a functional intrinsic clockwork. It is suggested that clock genes and their protein products may be directly involved in the daytime-dependent regulation and adaptation of hormone synthesis and release and within homeostatic adaptive plasticity.

scholarly journals Circadian rhythms in septic shock patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gunnar Lachmann ◽  
Bharath Ananthasubramaniam ◽  
Viktor A. Wünsch ◽  
Lara-Marie Scherfig ◽  
Clarissa von Haefen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Septic Shock ◽  
Immune Cells ◽  
Clock Gene ◽  
Clock Genes ◽  
Young Men ◽  
Time Of Day ◽  
Organ Injury ◽  
Control Group ◽  
Clock Gene Expression

Abstract Background Despite the intensive efforts to improve the diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock. Methods This prospective pilot study was performed at the university hospital Charité–Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 h over a 24-h period to isolate CD14-positive monocytes and to measure the expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. A rhythmicity score SP was calculated, which comprises values between -1 (arrhythmic) and 1 (rhythmic), and expression data were compared to data of a healthy study population additionally. Results 77% of the measured clock genes showed inconclusive rhythms, i.e., neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 ± 0.26) compared to the control group (12 healthy young men, 0.70 ± 0.18). In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls. Conclusion Molecular rhythms in immune cells of septic shock patients were substantially altered and decreased compared to healthy young men. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and down-regulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms. Trail registration Clinical trial registered with www.ClinicalTrials.gov (NCT02044575) on 24 January 2014.

scholarly journals Circadian Rhythms in Septic Shock Patients

2020 ◽  
Author(s):  
Gunnar Lachmann ◽  
Bharath Ananthasubramaniam ◽  
Viktor A. Wünsch ◽  
Lara-Marie Scherfig ◽  
Clarissa von Haefen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Septic Shock ◽  
Immune Cells ◽  
Clock Gene ◽  
Clock Genes ◽  
Time Of Day ◽  
University Hospital ◽  
Organ Injury ◽  
Control Group ◽  
Clock Gene Expression

Abstract Background: Although intensive efforts to improve diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock.Methods: This prospective pilot study was performed at the university hospital Charité – Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 hours over a 24-hour period to isolate CD14-positive monocytes and to measure expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. Expression data were compared to data of a healthy study population and a rhythmicity score SP was calculated, which comprises values between -1 (arrhythmic) and 1 (rhythmic). Results: Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 ± 0.26) compared to the control group (12 healthy young men, 0.70 ± 0.18). 77% of the measured clock genes were classified as having inconclusive rhythms, i.e. neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls.Conclusion: Compared to young healthy men, molecular rhythms in immune cells of septic shock patients were substantially decreased. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and downregulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms.Clinical trial registered with www.ClinicalTrials.gov (NCT02044575) on 24 January 2014.

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 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.

Abstract P639: Attenuation of Renal Inner Medullary Circadian Clock Gene Expression in Response to High Salt Intake is Dependent on the Endothelin B Receptor

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Joshua S Speed ◽  
Kelly A Hyndman ◽  
Malgorzata Kasztan ◽  
Jermaine G Johnston ◽  
Martin E Young ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Clock Gene ◽  
Salt Intake ◽  
Time Of Day ◽  
High Salt ◽  
Circadian Clock Gene ◽  
Clock Gene Expression ◽  
High Salt Intake ◽  
Renal Inner Medulla

Our lab has recently shown that ETB deficient (ETB def) rats have a time of day dependent impairment in their ability to excrete a Na+ load. These observations suggest an interaction between renal ETB receptors and circadian mechanisms that regulate renal tubular Na+ transport and excretion. Given that knockout of the circadian clock gene Bmal1 reduces blood pressure in mice, we hypothesized that a high salt intake impairs the clock mechanism in the renal inner medulla in an ETB dependent manner. Transgenic control (Tg con) or ETB def rats were fed normal (NS, 0.8% NaCl) or high (HS, 4% NaCl) salt for two weeks. In one group, rats were euthanized every 4 hours beginning at zeitgeber time 0 (lights on) for tissue collection (and subsequent assessment of circadian clock genes), while in a second group of rats urine was collected in 12-hour intervals (active vs. inactive). Consistent with our hypothesis, we observed that HS abolished the normal oscillation in Bmal1 expression in the renal inner medulla of Tg con rats, and effect not observed in ETB def rats. Interestingly, renal production of ET-1, was significantly higher during the active period vs. inactive period in both NS (3.6±1.1 vs. 0.8±0.2 pg/12hr respectively) and HS (9.2±4.1 vs. 1.6±0.3 pg/12hr respectively) fed Tg con rats. There was no time-of-day-dependent difference in ET-1 excretion in ETB def rats on NS (6.6±2.2 vs. 4.6±1.7 pg/12hr respectively), although this pattern was restored in ETB def rats fed HS (2.2±1.0 vs. 9.2±2.5 pg/12hr inactive vs. active). Taken together, these data indicate that an increase in renal ET-1/ETB activation in response to HS modulates inner medullary clock gene expression to promote renal Na+ excretion.

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 Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1522-1534 ◽  
Author(s):  
Elizabeth R. Woodruff ◽  
Lauren E. Chun ◽  
Laura R. Hinds ◽  
Robert L. Spencer
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Clock Gene ◽  
Expression Patterns ◽  
Time Of Day ◽  
Male Rat ◽  
Mrna Levels ◽  
Diurnal Pattern ◽  
Peripheral Tissues ◽  
Clock Gene Expression

Abstract Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation.

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