scholarly journals Functional Divergence of Mammalian TFAP2a and TFAP2b Transcription Factors for Bidirectional Sleep Control

Genetics ◽  
2020 ◽  
Vol 216 (3) ◽  
pp. 735-752
Author(s):  
Yang Hu ◽  
Alejandra Korovaichuk ◽  
Mariana Astiz ◽  
Henning Schroeder ◽  
Rezaul Islam ◽  
...  

Sleep is a conserved behavioral state. Invertebrates typically show quiet sleep, whereas in mammals, sleep consists of periods of nonrapid-eye-movement sleep (NREMS) and REM sleep (REMS). We previously found that the transcription factor AP-2 promotes sleep in Caenorhabditiselegans and Drosophila. In mammals, several paralogous AP-2 transcription factors exist. Sleep-controlling genes are often conserved. However, little is known about how sleep genes evolved from controlling simpler types of sleep to govern complex mammalian sleep. Here, we studied the roles of Tfap2a and Tfap2b in sleep control in mice. Consistent with our results from C. elegans and Drosophila, the AP-2 transcription factors Tfap2a and Tfap2b also control sleep in mice. Surprisingly, however, the two AP-2 paralogs play contrary roles in sleep control. Tfap2a reduction of function causes stronger delta and theta power in both baseline and homeostasis analysis, thus indicating increased sleep quality, but did not affect sleep quantity. By contrast, Tfap2b reduction of function decreased NREM sleep time specifically during the dark phase, reduced NREMS and REMS power, and caused a weaker response to sleep deprivation. Consistent with the observed signatures of decreased sleep quality, stress resistance and memory were impaired in Tfap2b mutant animals. Also, the circadian period was slightly shortened. Taken together, AP-2 transcription factors control sleep behavior also in mice, but the role of the AP-2 genes functionally diversified to allow for a bidirectional control of sleep quality. Divergence of AP-2 transcription factors might perhaps have supported the evolution of more complex types of sleep.

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A43-A44
Author(s):  
Michelle Persich ◽  
Sara Cloonan ◽  
Michael Grandner ◽  
William Killgore

Abstract Introduction Psychological resilience is the ability to withstand setbacks, adapt positively to challenges, and bounce back from the adversities of life. While the construct of resilience is broadly understood, the specific individual factors that contribute to the ability to be resilient and persevere in the face of difficulties remain poorly understood. We recently showed that psychological resilience during the COVID-19 pandemic was associated with a number of factors, including fewer complaints of insomnia, and others have suggested that sleep is an important contributor. We therefore tested the hypothesis that sleep quality and acute sleep quantity would combine to predict measures of psychological resilience and perseverance (i.e. “grit”). Methods We asked 447 adults (18–40 yrs; 72% female) to report the number of hours of sleep obtained the night before their assessment session (SLEEP), and complete several questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), the Connor-Davidson Resilience Scale (CD-RISC), Bartone Dispositional Resilience Scale (Hardiness), and the Grit Scale. Sleep metrics were used to predict resilience, hardiness, and grit using multiple linear regression. Results For resilience, PSQI (β=-.201, p<.00003) and SLEEP (β=.155, p<.001) each contributed uniquely to prediction of CD-RISC (R2=.08, p<.00001). Hardiness was also predicted (R2=.08, p<.00001) by a combination of PSQI (β=-.218, p<.00001) and SLEEP (β=.128, p=.007). Interestingly, worse sleep quality over the past month on the PSQI (β=.13, p=.008) in combination with more SLEEP the night before the assessment (β=.137, p=.005) each contributed uniquely to higher Grit (i.e., perseverance; R2=.03, p=.003). Conclusion Self-reported sleep quality and quantity were both independently associated with greater self-reported resilience, hardiness, and grit. While better sleep quality and more sleep the night before testing each uniquely predicted greater resilience and hardiness, a different pattern emerged for Grit. The combination of lower quality sleep over the past month followed by greater recent sleep duration was associated with increased perseverance. Whereas sleep quality appears to be more important for general resilience/hardiness, recent sleep time appears more important for the subjective perception of perseverance. Because these data are purely self-report and cross sectional, future work will need to determine the longitudinal effects on behavior. Support (if any):


SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Sjoerd J van Hasselt ◽  
Maria Rusche ◽  
Alexei L Vyssotski ◽  
Simon Verhulst ◽  
Niels C Rattenborg ◽  
...  

Abstract Most of our knowledge about the regulation and function of sleep is based on studies in a restricted number of mammalian species, particularly nocturnal rodents. Hence, there is still much to learn from comparative studies in other species. Birds are interesting because they appear to share key aspects of sleep with mammals, including the presence of two different forms of sleep, i.e. non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. We examined sleep architecture and sleep homeostasis in the European starling, using miniature dataloggers for electroencephalogram (EEG) recordings. Under controlled laboratory conditions with a 12:12 h light–dark cycle, the birds displayed a pronounced daily rhythm in sleep and wakefulness with most sleep occurring during the dark phase. Sleep mainly consisted of NREM sleep. In fact, the amount of REM sleep added up to only 1~2% of total sleep time. Animals were subjected to 4 or 8 h sleep deprivation to assess sleep homeostatic responses. Sleep deprivation induced changes in subsequent NREM sleep EEG spectral qualities for several hours, with increased spectral power from 1.17 Hz up to at least 25 Hz. In contrast, power below 1.17 Hz was decreased after sleep deprivation. Sleep deprivation also resulted in a small compensatory increase in NREM sleep time the next day. Changes in EEG spectral power and sleep time were largely similar after 4 and 8 h sleep deprivation. REM sleep was not noticeably compensated after sleep deprivation. In conclusion, starlings display signs of NREM sleep homeostasis but the results do not support the notion of important REM sleep functions.


Author(s):  
Arturo Laflor ◽  
Mabel Vazquez-Briseno ◽  
Fernanda Murillo-Munoz

<p class="Abstract">Computational sciences have gradually allowed scientists to develop novel technological projects to promote a healthy way of life. Most efforts have focus in promoting healthy diets and physical activity. Sleeping is also a crucial activity for humans. Poor sleep quality has adverse effects on health and might lead to physical and mental deterioration. Many computer systems have been used to measure sleep quantity and quality; however, there are few efforts to guide users about aspects that can influence sleeping. Sleep hygiene is a concept that allows controlling sleep-related habits and promoting good sleep quality; unfortunately, modern lifestyles can cause people to adopt wrong habits without being aware of their impact on sleep quality. This work describes a framework developed to guide user’s during the day in order to achieve good sleep quality during sleep time. A set of sleep hygiene factors (SHFs) intended to control hours before going to sleep was defined. The framework identifies personal SHFs using machine learning algorithms; furthermore, a new algorithm was designed to improve results. The framework also includes a mobile persuasive system to encourage users to control personal SHFs.</p>


2020 ◽  
Author(s):  
Ian Cook ◽  
Matlawa Mohlabe ◽  
Herbert Mabalane Makgopa

Abstract Objectives To investigate the relationship between objectively-measured, free-living sleep quantity and quality, and cardiometabolic health, in a rural African setting in 139 adults (≥40 years, female: n=99, male: n=40). Wrist-mounted, tri-axial accelerometry data was collected over nine days. Measures of sleep quantity and quality, and physical activity were extracted from valid minute-by-minute data. Self-reported data included behavioural, health and socio-demographic variables. Biological data included body composition, resting blood pressure and fasting blood glucose, insulin and lipids. Regression models were constructed with insulin resistance (IR), Cardiometabolic (CM) risk and a metabolic z-score, as dependent variables, adjusting for socio-demographic, behavioural and biological factors. Results Nocturnal sleep time was longer in females (p=0.054) and sleep quality was better in males (p≤0.017). Few participants slept >9 hours/night (4-5%), and 46-50% slept <7 hours/night. IR and CM risk was higher in females (p≤0.006). In adjusted models, sleep variables were independently associated with IR (p<0.05). Sleep quantity was linearly (p<0.05) and non-linearly (p≤0.0196) associated with IR, and non-linearly (p≤0.0398) associated with CM risk. Sleep quality was linearly related with IR (p<0.05). A number of non-sleep behavioural variables were independently associated with CM risk (alcohol and tobacco use, p≤0.034) and IR (physical activity, sugar-sweetened beverage consumption, p<0.05).


2021 ◽  
Author(s):  
Andrea L. Harris

There is currently mixed evidence for the relationship between poor sleep and daytime fatigue. It is well documented that retrospective measures of insomnia and fatigue are highly correlated with one another. However, other studies fail to demonstrate a link between objectively less sleep and fatigue; that is, individuals with shorter sleep times do not necessarily report increased fatigue. As such, the relationship between these two constructs remains unclear. The current investigation will help to elucidate the complex relationship between sleep and fatigue among those with and without insomnia by advancing the existing literature in two important ways. First, this study proposed to examine the temporal relationship between sleep and fatigue across two weeks, thereby investigating whether sleep and fatigue occur in accordance with one anotherover time. Second, this study utilized a multi-method approach by collecting subjective (i.e.,sleep diary) and objective (i.e., actigraphy) measures of sleep, as well as retrospective (i.e.,visual analogue scales: VAS) and prospective (i.e., momentary ratings) measures of fatigue. Two separate hierarchical linear models were used to test whether sleep (measured by sleep quality and total sleep time) predicted daytime fatigue on the VAS and actigraph, respectively. The secondary objective asked whether cognitive-behavioural variables (i.e., maladaptive sleep beliefs, fear and avoidance of fatigue, and fatigue-based rumination) may help account for the relationship between sleep and fatigue using mediation. The results of the primary analyses suggested that sleep quality significantly predicted VAS fatigue ratings, whereas total sleep time was a significant predictor of fatigue within- but not between-persons. No significant relationships were found between objective measures of sleep and momentary fatigue ratings. Finally, each of the cognitive-behavioural variables, with the exception of avoidance of fatigue, were significant mediators of the relationship between sleep and fatigue. The results demonstrated that compared to sleep quantity, our perception of sleep may play a more important role in predicting reports of daytime fatigue. These findings could help decrease the burden that individuals with insomnia place on their total sleep times, and instead, treatment could focus on challenging maladaptive sleep-related cognitions, which ultimately could lessen the overall sleep-related anxiety.


2020 ◽  
Author(s):  
Ian Cook ◽  
Matlawa Mohlabe ◽  
Herbert Mabalane Makgopa

Abstract Objectives To investigate the relationship between objectively-measured, free-living sleep quantity and quality, and cardiometabolic health, in a rural African setting in 139 adults (≥40 years, female: n=99, male: n=40). Wrist-mounted, tri-axial accelerometry data was collected over nine days. Measures of sleep quantity and quality, and physical activity were extracted from valid minute-by-minute data. Self-reported data included behavioural, health and socio-demographic variables. Biological data included body composition, resting blood pressure and fasting blood glucose, insulin and lipids. Logistic regression models were constructed with insulin resistance (IR) and Cardiometabolic (CM) risk, as dependent variables, adjusting for socio-demographic, behavioural and biological factors. Results Nocturnal sleep time was longer in females (p=0.054) and sleep quality was better in males (p≤0.017). Few participants slept >9 hours/night (4-5%), and 46-50% slept <7 hours/night. IR and CM risk was higher in females (p≤0.006). In adjusted models, sleep variables were independently associated with IR (p<0.05). Sleep quantity was non-linearly associated with CM risk (p≤0.0398), and linearly associated with IR (p≤0.0444). Sleep quality was linearly related with CM risk and IR (p≤0.0201). In several models, sleep quantity and sleep quality measures were concurrently and significantly associated with IR (p≤0.044).


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Ian Cook ◽  
Matlawa Mohlabe ◽  
Herbert Mabalane Makgopa

Abstract Objectives To investigate the relationship between objectively-measured, free-living sleep quantity and quality, and cardiometabolic health, in a rural African setting in 139 adults (≥40 years, female: n = 99, male: n = 40). Wrist-mounted, tri-axial accelerometry data was collected over 9 days. Measures of sleep quantity and quality, and physical activity were extracted from valid minute-by-minute data. Self-reported data included behavioural, health and socio-demographic variables. Biological data included body composition, resting blood pressure and fasting blood glucose, insulin and lipids. Logistic regression models were constructed with insulin resistance (IR) and cardiometabolic (CM) risk, as dependent variables, adjusting for socio-demographic, behavioural and biological factors. Results Nocturnal sleep time was longer in females (p = 0.054) and sleep quality was better in males (p ≤ 0.017). Few participants slept > 9 h/night (4–5%), and 46–50% slept < 7 h/night. IR and CM risk was higher in females (p ≤ 0.006). In adjusted models, sleep variables were independently associated with IR (p < 0.05). Sleep quantity was non-linearly associated with CM risk (p ≤ 0.0398), and linearly associated with IR (p ≤ 0.0444). Sleep quality was linearly related with CM risk and IR (p ≤ 0.0201). In several models, sleep quantity and sleep quality measures were concurrently and significantly associated with IR (p ≤ 0.044).


2021 ◽  
Author(s):  
Sheneé C Martin ◽  
Sean M Gay ◽  
Michael L Armstrong ◽  
Nila M Pazhayam ◽  
Nichole Reisdorph ◽  
...  

Sleep is an essential behavior that supports brain function and cognition throughout life, in part by acting on neuronal synapses. The synaptic signaling pathways that mediate the restorative benefits of sleep are not fully understood, particularly in the context of development. Endocannabinoids (eCBs) including 2-arachidonyl glycerol (2-AG) and anandamide (AEA), are bioactive lipids that activate cannabinoid receptor, CB1, to regulate synaptic transmission and mediate cognitive functions and many behaviors, including sleep. We used targeted mass spectrometry to measure changes in forebrain synaptic eCBs during the sleep/wake cycle in developing and adult mice. We find that eCBs are downregulated in response to acute sleep deprivation in juvenile mice, while in young adults eCBs are upregulated during the sleep phase in a circadian manner. Next we manipulated the eCB system using selective pharmacology and measured the effects on sleep behavior in developing and adult mice of both sexes using a non-invasive piezoelectric home-cage recording apparatus. Enhancement of eCB signaling through inhibition of 2-AG or AEA degradation, increased dark phase sleep amount and bout length in developing and adult males, but not in females. Inhibition of CB1 by injection of the antagonist AM251 reduced sleep time and caused sleep fragmentation in developing and adult males and females. Our data suggest that males are more sensitive to the sleep promoting effects of enhanced eCBs but that tonic eCB signaling supports sleep behavior through multiple stages of development in both sexes. This work informs the further development of cannabinoid-based therapeutics for sleep disruption.


2021 ◽  
Author(s):  
Andrea L. Harris

There is currently mixed evidence for the relationship between poor sleep and daytime fatigue. It is well documented that retrospective measures of insomnia and fatigue are highly correlated with one another. However, other studies fail to demonstrate a link between objectively less sleep and fatigue; that is, individuals with shorter sleep times do not necessarily report increased fatigue. As such, the relationship between these two constructs remains unclear. The current investigation will help to elucidate the complex relationship between sleep and fatigue among those with and without insomnia by advancing the existing literature in two important ways. First, this study proposed to examine the temporal relationship between sleep and fatigue across two weeks, thereby investigating whether sleep and fatigue occur in accordance with one anotherover time. Second, this study utilized a multi-method approach by collecting subjective (i.e.,sleep diary) and objective (i.e., actigraphy) measures of sleep, as well as retrospective (i.e.,visual analogue scales: VAS) and prospective (i.e., momentary ratings) measures of fatigue. Two separate hierarchical linear models were used to test whether sleep (measured by sleep quality and total sleep time) predicted daytime fatigue on the VAS and actigraph, respectively. The secondary objective asked whether cognitive-behavioural variables (i.e., maladaptive sleep beliefs, fear and avoidance of fatigue, and fatigue-based rumination) may help account for the relationship between sleep and fatigue using mediation. The results of the primary analyses suggested that sleep quality significantly predicted VAS fatigue ratings, whereas total sleep time was a significant predictor of fatigue within- but not between-persons. No significant relationships were found between objective measures of sleep and momentary fatigue ratings. Finally, each of the cognitive-behavioural variables, with the exception of avoidance of fatigue, were significant mediators of the relationship between sleep and fatigue. The results demonstrated that compared to sleep quantity, our perception of sleep may play a more important role in predicting reports of daytime fatigue. These findings could help decrease the burden that individuals with insomnia place on their total sleep times, and instead, treatment could focus on challenging maladaptive sleep-related cognitions, which ultimately could lessen the overall sleep-related anxiety.


2011 ◽  
Vol 300 (4) ◽  
pp. R885-R894 ◽  
Author(s):  
Irma Gvilia ◽  
Natalia Suntsova ◽  
Bryan Angara ◽  
Dennis McGinty ◽  
Ronald Szymusiak

The present study evaluated the hypothesis that developmental changes in hypothalamic sleep-regulatory neuronal circuits contribute to the maturation of sleep homeostasis in rats during the fourth postnatal week. In a longitudinal study, we quantified electrographic measures of sleep during baseline and in response to sleep deprivation (SD) on postnatal days 21/29 (P21/29) and P22/30 ( experiment 1). During 24-h baseline recordings on P21, total sleep time (TST) during the light and dark phases did not differ significantly. On P29, TST during the light phase was significantly higher than during the dark phase. Mean duration of non-rapid-eye-movement (NREM) sleep bouts was significantly longer on P29 vs. P21, indicating improved sleep consolidation. On both P22 and P30, rats exhibited increased NREM sleep amounts and NREM electroencephalogram delta power during recovery sleep (RS) compared with baseline. Increased NREM sleep bout length during RS was observed only on P30. In experiment 2, we quantified activity of GABAergic neurons in median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) during SD and RS in separate groups of P22 and P30 rats using c-Fos and glutamic acid decarboxylase (GAD) immunohistochemistry. In P22 rats, numbers of Fos+GAD+ neurons in VLPO did not differ among experimental conditions. In P30 rats, Fos+GAD+ counts in VLPO were elevated during RS. MnPN neuronal activity was state-dependent in P22 rats, but Fos+GAD+ cell counts were higher in P30 rats. These findings support the hypothesis that functional emergence of preoptic sleep-regulatory neurons contributes to the maturation of sleep homeostasis in the developing rat brain.


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