scholarly journals Sexually dimorphic influence of the circadian clock gene Bmal1 in the striatum on alcohol intake

2020 ◽  
Author(s):  
Nuria de Zavalia ◽  
Konrad Schoettner ◽  
Jory A. Goldsmith ◽  
Pavel Solis ◽  
Sarah Ferraro ◽  
...  
Keyword(s):  
Sex Differences ◽  
Alcohol Consumption ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Alcohol Intake ◽  
Clock Gene ◽  
Conditional Knockout ◽  
Mammalian Brain ◽  
Sexually Dimorphic ◽  
The Impact

SummaryThe gene Bmal1 (brain and muscle Arnt-like 1) plays an obligatory role in the generation of circadian rhythms in the suprachiasmatic nucleus (SCN), the master circadian clock in mammals [1–5]. Notably, Bmal1 is widely expressed in mammalian brain [6], and perturbations in Bmal1 expression in select forebrain regions cause behavioral disturbances that are independent of the SCN, such as disturbances in sleep architecture, and in cognitive and affective behaviors [1, 7–15]. Interestingly, gene association studies in humans and in animals suggest that Bmal1 may influence the propensity to consume alcohol, and that polymorphisms in Bmal1 may confer risk for alcohol dependence and related disorders [16–20]. However, research has not yet provided evidence of a causal role of Bmal1 in the control of alcohol intake. We investigated voluntary alcohol consumption in conditional knockout mice that lack Bmal1 exclusively in the striatum, which is an important structure in the control of alcohol intake and preference [21–26]. Experiments were carried out in both male and female mice in order to account for the known sex differences in alcohol consumption [27–31] and in striatal functioning [32–36], as well as in the expression of clock genes and in the impact of circadian clocks on behavior [37–44]. We found that, in both males and females, selective deletion of Bmal1 from principal medium spiny neurons (MSNs) of the striatum significantly altered voluntary alcohol intake and preference. Strikingly, the effect of Bmal1 deletion was sexually dimorphic. Whereas in males, deletion of Bmal1 augmented alcohol intake and preference, in females, the same deletion suppressed alcohol intake and preference. Interestingly, striatal deletion of the clock gene Per2, which interacts with Bmal1 in the generation of circadian rhythms [4], and which has been shown to affect alcohol consumption in male mice [45], mimicked the effect of Bmal1 deletion, albeit only in males. These results show that Bmal1 in MSNs of the striatum exerts a sexually dimorphic influence on alcohol intake in mice, moderating intake in males, possibly via Per2, and promoting heightened intake in females, independently of Per2. We propose that a sexually dimorphic mechanism in the function of Bmal1 in the striatum contributes to sex differences in the propensity to consume alcohol in mice. Whether such mechanism contributes to sex differences in other striatum-dependent appetitive and consummatory behaviors remains to be investigated.

Norwegians and cheap alcohol: Consumption in a low price area

1994 ◽  
Vol 11 (3) ◽  
pp. 139-145
Author(s):  
Georg Høyer ◽  
Odd Nilssen ◽  
Tormod Brenn ◽  
Helge Schirmer
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Intake ◽  
Alcohol Policy ◽  
Average Amount ◽  
Self Reports ◽  
Frequency Of Alcohol Intake ◽  
The Impact ◽  
Self Administered Questionnaire

Although the archipelago of Svalbard is a part of Norway (situated 78 degrees north), the area is subject to a different alcohol policy than on the Norwegian mainland. In Svalbard, the prices of alcohol are low (in comparison to those on the mainland): however, personal quotas are in force in order to control sales. This study compares the level of alcohol consumption on Svalbard and on the Norwegian mainland. The comparison is based on self-reports of alcohol consumption. In Svalbard all of the residents eighteen years or older were screened by a self-administered questionnaire: alcohol consumption was recorded as an intake of alcohol measured in units during the last week before filling in the questionnaire. On the mainland, the recording was carried out through personal interviews in which respondents were asked about the frequency of alcohol intake and the average amount of intake for each episode in representative periods. The results showed that men in Svalbard consumed 1.7 times more alcohol then the men consumed on the mainland: women, 1.4 times more. The increased level of alcohol consumption can primarily be explained by the lower prices of alcohol in Svalbard. Thus this study strongly confirms the results of other studies which stress the impact of prices on the levels of alcohol consumption.

scholarly journals Re-Setting the Circadian Clock Using Exercise against Sarcopenia

2020 ◽  
Vol 21 (9) ◽  
pp. 3106 ◽  
Author(s):  
Youngju Choi ◽  
Jinkyung Cho ◽  
Mi-Hyun No ◽  
Jun-Won Heo ◽  
Eun-Jeong Cho ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Intervention Strategy ◽  
Muscle Metabolism ◽  
Circadian Disruption ◽  
Adverse Health Outcomes ◽  
Exercise Timing ◽  
Underlying Mechanisms ◽  
The Impact

Sarcopenia is defined as the involuntary loss of skeletal muscle mass and function with aging and is associated with several adverse health outcomes. Recently, the disruption of regular circadian rhythms, due to shift work or nocturnal lifestyle, is emerging as a novel deleterious factor for the development of sarcopenia. The underlying mechanisms responsible for circadian disruption-induced sarcopenia include molecular circadian clock and mitochondrial function associated with the regulation of circadian rhythms. Exercise is a potent modulator of skeletal muscle metabolism and is considered to be a crucial preventative and therapeutic intervention strategy for sarcopenia. Moreover, emerging evidence shows that exercise, acting as a zeitgeber (time cue) of the skeletal muscle clock, can be an efficacious tool for re-setting the clock in sarcopenia. In this review, we provide the evidence of the impact of circadian disruption on skeletal muscle loss resulting in sarcopenia. Furthermore, we highlight the importance of exercise timing (i.e., scheduled physical activity) as a novel therapeutic strategy to target circadian disruption in skeletal muscle.

scholarly journals Growth Hormone Pulses and Liver Gene Expression Are Differentially Regulated by the Circadian Clock Gene Bmal1

Endocrinology ◽  
2021 ◽  
Vol 162 (4) ◽  
Author(s):  
Erica L Schoeller ◽  
Karen J Tonsfeldt ◽  
McKenna Sinkovich ◽  
Rujing Shi ◽  
Pamela L Mellon
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Circadian Clock ◽  
Messenger Rna ◽  
Clock Gene ◽  
Serum Insulin ◽  
Sexually Dimorphic ◽  
Circadian Clock Gene ◽  
Major Urinary Proteins ◽  
Hepatic Genes

Abstract In this study, we found that loss of the circadian clock gene Bmal1 causes disruptions throughout the growth hormone (GH) axis, from hepatic gene expression to production of urinary pheromones and pheromone-dependent behavior. First, we show that Bmal1 knockout (KO) males elicit reduced aggressive responses from wild-type (WT) males and secrete lower levels of major urinary proteins (MUPs); however, we also found that a liver-specific KO of Bmal1 (liver-Bmal1-KO) produces a similar reduction in MUP secretion without a defect in aggressive behavior, indicating that the decrease in elicited aggression arises from another factor. We then shifted our investigation to determine the cause of MUP dysregulation in Bmal1 KO animals. Because the pulse pattern of GH drives sexually dimorphic expression of hepatic genes including MUPs, we examined GH pulsatility. We found that Bmal1 KO males have a female-like pattern of GH release, whereas liver-Bmal1-KO mice are not significantly different from either WT or Bmal1 KO. Since differential patterns of GH release regulate the transcription of many sexually dimorphic genes in the liver, we then examined hepatic gene transcription in Bmal1 KO and liver-Bmal1-KO mice. We found that while some female-predominant genes increase in the Bmal1 KO, there was no decrease in male-predominant genes, and little change in the liver-Bmal1-KO. We also found disrupted serum insulin growth factor 1 (IGF-1) and liver Igf1 messenger RNA in the Bmal1 KO mice, which may underlie the disrupted GH release. Overall, our findings differentiate between GH-pulse–driven and circadian-driven effects on hepatic genes, and the functional consequences of altered GH pulsatility.

scholarly journals Sex-Dependent Effects of Chronic Microdrive Implantation on Acquisition of Trace Eyeblink Conditioning

2021 ◽  
Author(s):  
Amy P Rapp ◽  
Timothy J Hark ◽  
John M Power ◽  
M Matthew Oh ◽  
Jeffrey N Savas ◽  
...  
Keyword(s):  
Sex Differences ◽  
Associative Learning ◽  
Mapk Pathway ◽  
Eyeblink Conditioning ◽  
Sexually Dimorphic ◽  
Male Mice ◽  
Tandem Mass Tag ◽  
The Impact ◽  
Trace Eyeblink Conditioning

Neuroscience techniques, including in vivo recording, have allowed for a great expansion in knowledge; however, this technology may also affect the very phenomena researchers set out to investigate. Including both female and male mice in our associative learning experiments shed light on sex differences on the impact of chronic implantation of tetrodes on learning. While previous research showed intact female mice acquired trace eyeblink conditioning faster than male and ovariectomized females, implantation of chronic microdrive arrays showed sexually dimorphic effects on learning. Microdrive implanted male mice acquired the associative learning paradigm faster than both intact and ovariectomized females. These effects were not due to the weight of the drive alone, as there were no significant sex-differences in learning of animals that received dummy drive implants without tetrodes lowered into the brain. Tandem mass tag mass spectrometry and western blot analysis suggest that significant alterations in the MAPK pathway, acute inflammation, and brain derived neurotrophic factor may underlie these observed sex- and surgery-dependent effects on learning.

Changing University Students’ Alcohol Culture with a web-based intervention: Clustered Randomized Controlled Trial (Preprint)

2020 ◽  
Author(s):  
Jane Greve ◽  
Rune Vammen Lesner ◽  
Stefan Bastholm Andrade
Keyword(s):  
Alcohol Consumption ◽  
University Students ◽  
Alcohol Intake ◽  
Intervention Group ◽  
Control Group ◽  
First Year Students ◽  
Personal Benefit ◽  
Drinking Culture ◽  
The University ◽  
The Impact

BACKGROUND In most Western countries, excessive alcohol intake among university students is a cause of concern. The majority of students view drinking as a cornerstone of university life, and many find it difficult to go against the dominant drinking culture. While digital health interventions have been shown to reduce drinking among university students, no intervention has been aimed at changing the overall university drinking culture. This intervention provided the students with tools that helped them make pre-commitment strategies and change their views on the social norms that prevent excessive alcohol intake. OBJECTIVE Our objective is to evaluate the impact of an intervention aimed at reducing the excessive drinking culture among Danish university students. As a secondary outcome, we measured the impact of the intervention on two individual motivational factors for participating in the drinking culture at the university: alcohol consumption as both a personal benefit and a facilitator of socialization. METHODS To evaluate the impact of the intervention, we conducted a cluster randomized controlled experiment among university students at Aarhus University. The students were stratified by gender and self-reported binge drinking. Each student was assigned to either a control or an intervention group. A baseline questionnaire was sent to the participants when school started in September 2019, and a follow-up questionnaire was sent out two months later. The primary outcomes were measured with the Alcohol Use Disorder Identification Test (questions 1-3). To examine the mechanisms underlying the effect, we analyzed two motivational factors for participating in the drinking culture at the university: alcohol consumption as both and a personal benefit and a facilitator of socialization. RESULTS In total 961 students signed up, and 509 of them completed the follow-up questionnaire. Compared to the students in the control group, the students in the intervention group had a 15.8% (P<.001) reduction on their monthly level of alcohol intake two months after the intervention. The result is driven by a large effect on male and first-year students. The intervention had no effect on binge drinking, alcohol addiction, or severely harmful alcohol consumption. Our results also showed that while the students in the intervention group found it less difficult to say “no” to drinking there were no difference in the assessment of being part of the student environment between the students in the intervention and control Group. CONCLUSIONS The intervention had a significant and reducing impact on the students’ monthly alcohol intake. That the effect of the intervention was largest among the young and first-year students, who will be the responsible for the drinking culture at the University in the coming years, suggest that small nudging-based interventions can potentially have significant long-term beneficial effects. CLINICALTRIAL American Economic Association’s registry for randomized trials with RCT ID: AEARCTR-0004703. https://www.socialscienceregistry.org/trials/4703.

Alcohol Consumption is Associated With An Increased Risk of Microscopic Colitis: Results From 2 Prospective US Cohort Studies

2021 ◽  
Author(s):  
Blake Niccum ◽  
Kevin Casey ◽  
Kristin Burke ◽  
Emily W Lopes ◽  
Paul Lochhead ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Intake ◽  
Cox Proportional Hazards ◽  
Dietary Factors ◽  
Microscopic Colitis ◽  
Health Study ◽  
Higher Alcohol ◽  
Increased Risk ◽  
Incident Cases ◽  
The Impact

Abstract Background No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC. Methods We conducted a prospective cohort study of 209,902 participants (age range, 28.5–66.7 years) enrolled in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend &lt; .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86–1.67) for consumers of 0.1–4.9 g/day of alcohol, 1.90 (95% CI, 1.34–2.71) for consumers of 5–14.9 g/day, and 2.31 (95% CI, 1.54–3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04–1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91–1.12) or liquor (aHR, 1.00; 95% CI, 0.92–1.09). Conclusions Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.

scholarly journals Development of diabetes does not alter behavioral and molecular circadian rhythms in a transgenic rat model of type 2 diabetes mellitus

2017 ◽  
Vol 313 (2) ◽  
pp. E213-E221 ◽  
Author(s):  
Jingyi Qian ◽  
Anthony P. Thomas ◽  
Analyne M. Schroeder ◽  
Kuntol Rakshit ◽  
Christopher S. Colwell ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Rat Model ◽  
Clock Gene ◽  
Transgenic Rat ◽  
Circadian Activity ◽  
Melatonin Secretion ◽  
Clock Gene Expression

Metabolic state and circadian clock function exhibit a complex bidirectional relationship. Circadian disruption increases propensity for metabolic dysfunction, whereas common metabolic disorders such as obesity and type 2 diabetes (T2DM) are associated with impaired circadian rhythms. Specifically, alterations in glucose availability and glucose metabolism have been shown to modulate clock gene expression and function in vitro; however, to date, it is unknown whether development of diabetes imparts deleterious effects on the suprachiasmatic nucleus (SCN) circadian clock and SCN-driven outputs in vivo. To address this question, we undertook studies in aged diabetic rats transgenic for human islet amyloid polypeptide, an established nonobese model of T2DM (HIP rat), which develops metabolic defects closely recapitulating those present in patients with T2DM. HIP rats were also cross-bred with a clock gene reporter rat model (Per1:luciferase transgenic rat) to permit assessment of the SCN and the peripheral molecular clock function ex vivo. Utilizing these animal models, we examined effects of diabetes on 1) behavioral circadian rhythms, 2) photic entrainment of circadian activity, 3) SCN and peripheral tissue molecular clock function, and 4) melatonin secretion. We report that circadian activity, light-induced entrainment, molecular clockwork, as well as melatonin secretion are preserved in the HIP rat model of T2DM. These results suggest that despite the well-characterized ability of glucose to modulate circadian clock gene expression acutely in vitro, SCN clock function and key behavioral and physiological outputs appear to be preserved under chronic diabetic conditions characteristic of nonobese T2DM.

Heavy drinking habits are associated with worse in-hospital outcomes in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Tersalvi ◽  
L Biasco ◽  
D Radovanovic ◽  
H Rickli ◽  
M Roffi ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Hospital Mortality ◽  
Alcohol Intake ◽  
Funding Source ◽  
Hospital Outcomes ◽  
Coronary Syndrome ◽  
Daily Alcohol Intake ◽  
Heavy Alcohol Consumption ◽  
The Impact ◽  
Regular Alcohol Consumption

Abstract Introduction The association between alcohol consumption and the occurrence of coronary heart disease is well described in literature. Data regarding the impact of regular alcohol consumption on in-hospital outcomes in the setting of acute coronary syndrome (ACS) are lacking. Purpose We aimed to evaluate the impact of self-reported alcohol consumption on in-hospital outcomes in patients with ACS. Methods Data derived from patients enrolled between 2007 and 2019 in the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry were retrospectively analyzed. The primary endpoint was all-cause in-hospital mortality, while secondary endpoints were set as incidence of major adverse cardiac and cerebrovascular events (MACCEs). Outcomes comparisons according to quantity of daily alcohol intake were also performed. Results Records concerning alcohol consumption were available in 25707 patients; 5298 of them (21%) fulfilled the criteria of regular alcohol consumption. Daily alcohol intake was reported in 4059 (77%), of these patients (regular drinkers) with 2640 light drinkers (≤2 drinks/day) and 1419 heavy drinkers (&gt;2 drinks/day). Regular drinkers were predominantly male, younger, smokers, more comorbid and with a worse clinical presentation as compared to abstainers/occasional drinkers. In-hospital mortality and MACCEs of heavy drinkers were significantly higher compared to light drinkers (5.4% vs. 3.3% and 7.0% vs. 4.4%, both p=0.001). When tested together with GRACE risk score parameters, heavy alcohol consumption was independently associated to in-hospital mortality (p=0.004). Conclusions Heavy alcohol consumption is an additional independent predictor of in-hospital mortality in patients presenting with ACS. Figure 1. Study flowchart. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Swiss Heart Foundation

scholarly journals The 2020 Pittendrigh/Aschoff Lecture: My Circadian Journey

2021 ◽  
pp. 074873042098239
Author(s):  
Amita Sehgal
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Education System ◽  
Clock Gene ◽  
Immigrant Woman ◽  
Postdoctoral Fellow ◽  
The Us ◽  
Science And Education ◽  
Clock Mechanism

The circadian field has come a long way since I started as a postdoctoral fellow ~30 years ago. At the time, the only known animal clock gene was period, so I had the privilege of witnessing, and participating in, the molecular revolution that took us from the discovery of the circadian clock mechanism to the identification of pathways that link clocks to behavior and physiology. This lecture highlights my role and perspective in these developments, and also demonstrates how the successful use of Drosophila for studies of circadian rhythms inspired us to develop a fly model for sleep. I also touch upon my experiences as a non-white immigrant woman navigating my way through the US science and education system, and hope my story will be of interest to some.

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