Neurobiology of Sleep and Circadian Rhythms最新文献

{"title":"Ontogenesis of the molecular response to sleep loss","authors":"Christine M. Muheim ,&nbsp;Kaitlyn Ford ,&nbsp;Elizabeth Medina ,&nbsp;Kristan Singletary ,&nbsp;Lucia Peixoto ,&nbsp;Marcos G. Frank","doi":"10.1016/j.nbscr.2023.100092","DOIUrl":"10.1016/j.nbscr.2023.100092","url":null,"abstract":"<div><p>Sleep deprivation (SD) results in profound cellular and molecular changes in the adult mammalian brain. Some of these changes may result in, or aggravate, brain disease. However, little is known about how SD impacts gene expression in developing animals. We examined the transcriptional response in the prefrontal cortex (PFC) to SD across postnatal development in male mice. We used RNA sequencing to identify functional gene categories that were specifically impacted by SD. We find that SD has dramatically different effects on PFC genes depending on developmental age. Gene expression differences after SD fall into 3 categories: present at all ages (conserved), present when mature sleep homeostasis is first emerging, and those unique to certain ages. Developmentally conserved gene expression was limited to a few functional categories, including Wnt-signaling which suggests that this pathway is a core mechanism regulated by sleep. In younger ages, genes primarily related to growth and development are affected while changes in genes related to metabolism are specific to the effect of SD in adults.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068260/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9765223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of sleep when it is needed most – Consequences of persistent developmental sleep disruption: A scoping review of rodent models","authors":"Noah E.P. Milman ,&nbsp;Carolyn E. Tinsley ,&nbsp;Ravikiran M. Raju ,&nbsp;Miranda M. Lim","doi":"10.1016/j.nbscr.2022.100085","DOIUrl":"10.1016/j.nbscr.2022.100085","url":null,"abstract":"<div><p>Sleep is an essential component of development. Developmental sleep disruption (DSD) impacts brain maturation and has been associated with significant consequences on socio-emotional development. In humans, poor sleep during infancy and adolescence affects neurodevelopmental outcomes and may be a risk factor for the development of autism spectrum disorder (ASD) or other neuropsychiatric illness. Given the wide-reaching and enduring consequences of DSD, identifying underlying mechanisms is critical to best inform interventions with translational capacity. In rodents, studies have identified some mechanisms and neural circuits by which DSD causes later social, emotional, sensorimotor, and cognitive changes. However, these studies spanned methodological differences, including different developmental timepoints for both sleep disruption and testing, different DSD paradigms, and even different rodent species. In this scoping review on DSD in rodents, we synthesize these various studies into a cohesive framework to identify common neural mechanisms underlying DSD-induced dysfunction in brain and behavior. Ultimately, this review serves the goal to inform the generation of novel translational interventions for human developmental disorders featuring sleep disruption.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4b/98/main.PMC9768382.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9999871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repetitive mild traumatic brain injury alters central and peripheral clock gene expression in the adolescent rat","authors":"Marissa Sgro ,&nbsp;Susanne Ellens ,&nbsp;Zoe N. Kodila ,&nbsp;Jennaya Christensen ,&nbsp;Crystal Li ,&nbsp;Richelle Mychasiuk ,&nbsp;Glenn R. Yamakawa","doi":"10.1016/j.nbscr.2023.100090","DOIUrl":"10.1016/j.nbscr.2023.100090","url":null,"abstract":"<div><p>Mild traumatic brain injury (mTBI) or concussion is a common injury worldwide leading to substantial medical costs and a high burden on society. In adolescents, falls and sports related trauma are often the causes of mTBI. Importantly, critical brain growth and development occurs during this sensitive period making the prospect of a brain injury a worrying phenomenon. Upwards of 70% of patients report circadian disruption following these injuries and this has been shown to impede recovery. Therefore, we sought to determine if core circadian clock gene expression was disrupted in rat model of repetitive mTBI (RmTBI). Male and female adolescent rats (n = 129) received sham or RmTBI. The animals were then euthanized at different times throughout the day and night. Tissue from the hypothalamus, cerebellum, hippocampus, liver, and small intestine were evaluated for the expression of <em>per1, per2, cry1, clock, bmal1</em> and <em>rev-erb-α</em>. We found most clock genes varied across the day/night indicating circadian expression patterns. In the hypothalamus we found RmTBI altered the expression of <em>cry1</em> and bmal1 in addition to sex differences in <em>per2, cry1, clock, bmal1</em> and <em>rev-erb- α</em>. In the cerebellum, <em>per1</em>, <em>per2</em>, <em>cry1</em>, <em>clock</em>, <em>bmal1</em> and <em>rev-erb-α</em> rhythms were all knocked out by RmTBI in addition to sex differences in <em>cry1</em>, <em>clock</em> and <em>bmal1</em> expression. We also detected a significant decrease in overall expression of all clock genes in males in the middle of the night. In the hippocampus we found that RmTBI changed the rhythm of rev-erb-α expression in addition to sex differences in <em>bmal1</em> expression. In the liver we detected strong rhythms in all genes examined, however only <em>per2</em> expression was knocked out by RmTBI, in addition we also detected sex differences in <em>per2</em> and <em>cry1</em>. We also detected an overall decrease in female clock gene expression in the early night. In the small intestine, RmTBI altered <em>cry1</em> expression and there were sex differences in <em>rev-erb-α</em>. These results indicate that RmTBI alters core circadian clock gene expression in the central and peripheral nervous system in a time, tissue and sex dependent manner. This may be disrupting important phase relationships between the brain and peripheral nervous system and contributing to post-injury symptomology and also highlights the importance for time and sex dependent assessment of injury outcomes.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/00/main.PMC10024151.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9509312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian profile, daytime activity, and the Parkinson's phenotype: A motion sensor pilot study with neurobiological underpinnings","authors":"Massimo Marano ,&nbsp;Jessica Rosati ,&nbsp;Alessandro Magliozzi ,&nbsp;Alessia Casamassa ,&nbsp;Alessia Rappa ,&nbsp;Gabriele Sergi ,&nbsp;Miriam Iannizzotto ,&nbsp;Ziv Yekutieli ,&nbsp;Angelo Luigi Vescovi ,&nbsp;Vincenzo Di Lazzaro","doi":"10.1016/j.nbscr.2023.100094","DOIUrl":"10.1016/j.nbscr.2023.100094","url":null,"abstract":"<div><p>Circadian rhythm impairment may play a role in Parkinson's disease (PD) pathophysiology. Recent literature associated circadian rhythm features to the risk of developing Parkinson and to its progression through stages. The association between the chronotype and the phenotype should be verified on a clinical and biological point of view. Herein we investigate the chronotype of a sample of 50 PD patients with the Morningness Eveningness Questionnaire and monitor their daily activity with a motion sensor embedded in a smartphone. Fibroblasts were collected from PD patients (n = 5) and from sex/age matched controls (n = 3) and tested for the circadian expression of clock genes (CLOCK, BMAL1, PER1, CRY1), and for cell morphology, proliferation, and death. Our results show an association between the chronotype and the PD phenotype. The most representative clinical chronotypes were “moderate morning” (56%), the “intermediate” (24%) and, in a minor part, the “definite morning” (16%). They differed for axial motor impairment, presence of motor fluctuations and quality of life (p &lt; 0.05). Patients with visuospatial dysfunction and patients with a higher PIGD score had a blunted motor daily activity (p = 0.006 and p = 0.001, respectively), independently by the influence of age and other motor scores. Fibroblasts obtained by PD patients (n = 5) had an impaired BMAL1 cycle compared to controls (n = 3, p = 0.01). Moreover, a PD flat BMAL1 profile was associated with the lowest cell proliferation and the largest cell morphology. This study contributes to the growing literature on CR abnormalities in the pathophysiology of Parkinson's disease providing a link between the clinical and biological patient chronotype and the disease phenomenology.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070882/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9324569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracting continuous sleep depth from EEG data without machine learning","authors":"Claus Metzner ,&nbsp;Achim Schilling ,&nbsp;Maximilian Traxdorf ,&nbsp;Holger Schulze ,&nbsp;Konstantin Tziridis ,&nbsp;Patrick Krauss","doi":"10.1016/j.nbscr.2023.100097","DOIUrl":"10.1016/j.nbscr.2023.100097","url":null,"abstract":"<div><p>The human sleep-cycle has been divided into discrete sleep stages that can be recognized in electroencephalographic (EEG) and other bio-signals by trained specialists or machine learning systems. It is however unclear whether these human-defined stages can be re-discovered with unsupervised methods of data analysis, using only a minimal amount of generic pre-processing. Based on EEG data, recorded overnight from sleeping human subjects, we investigate the degree of clustering of the sleep stages using the General Discrimination Value as a quantitative measure of class separability. Virtually no clustering is found in the raw data, even after transforming the EEG signals of each 30-s epoch from the time domain into the more informative frequency domain. However, a Principal Component Analysis (PCA) of these epoch-wise frequency spectra reveals that the sleep stages separate significantly better in the low-dimensional sub-space of certain PCA components. In particular the component <em>C</em>₁(<em>t</em>) can serve as a robust, continuous ‘master variable’ that encodes the depth of sleep and therefore correlates strongly with the ‘hypnogram’, a common plot of the discrete sleep stages over time. Moreover, <em>C</em>₁(<em>t</em>) shows persistent trends during extended time periods where the sleep stage is constant, suggesting that sleep may be better understood as a continuum. These intriguing properties of <em>C</em>₁(<em>t</em>) are not only relevant for understanding brain dynamics during sleep, but might also be exploited in low-cost single-channel sleep tracking devices for private and clinical use.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10238579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9637822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep disturbances in autism spectrum disorder: Animal models, neural mechanisms, and therapeutics","authors":"John J. Maurer ,&nbsp;Ashley Choi ,&nbsp;Isabella An,&nbsp;Nicholas Sathi,&nbsp;Shinjae Chung","doi":"10.1016/j.nbscr.2023.100095","DOIUrl":"10.1016/j.nbscr.2023.100095","url":null,"abstract":"<div><p>Sleep is crucial for brain development. Sleep disturbances are prevalent in children with autism spectrum disorder (ASD). Strikingly, these sleep problems are positively correlated with the severity of ASD core symptoms such as deficits in social skills and stereotypic behavior, indicating that sleep problems and the behavioral characteristics of ASD may be related. In this review, we will discuss sleep disturbances in children with ASD and highlight mouse models to study sleep disturbances and behavioral phenotypes in ASD. In addition, we will review neuromodulators controlling sleep and wakefulness and how these neuromodulatory systems are disrupted in animal models and patients with ASD. Lastly, we will address how the therapeutic interventions for patients with ASD improve various aspects of sleep. Together, gaining mechanistic insights into the neural mechanisms underlying sleep disturbances in children with ASD will help us to develop better therapeutic interventions.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/c8/main.PMC10176270.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9704736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep across the first year of life is prospectively associated with brain volume in 12-months old infants","authors":"Katharina Pittner ,&nbsp;Jerod Rasmussen ,&nbsp;Miranda M. Lim ,&nbsp;John H. Gilmore ,&nbsp;Martin Styner ,&nbsp;Sonja Entringer ,&nbsp;Pathik D. Wadhwa ,&nbsp;Claudia Buss","doi":"10.1016/j.nbscr.2023.100091","DOIUrl":"10.1016/j.nbscr.2023.100091","url":null,"abstract":"<div><h3>Objective</h3><p>Longer sleep duration in infancy supports cognitive and affective functioning – likely through effects on brain development. From childhood through old age, there is evidence for a close link between sleep and brain volume. However, little is known about the association between sleep duration and brain volume in infancy, a developmental period of unprecedented brain maturation. This study aimed to close this gap by assessing sleep duration across the first year of life and gray and white matter volume at 12-mo age.</p></div><div><h3>Method</h3><p>Infant sleep duration trajectories across the first year of life were based on maternal reports at 1, 3, 6, 9, and 12 months of age. Infant specific trajectories were generated by running a logarithmic regression for each infant and residualizing the resulting slopes for their intercept. Structural magnetic resonance imaging (MRI) scans were acquired at 12-mo age. Gray and white matter volume estimates were residualized for intracranial volume and age at scan.</p></div><div><h3>Results</h3><p>Data to calculate sleep trajectories was available for 112 infants. Overall, sleep duration decreased over the course of the first year of life and was best described by a logarithmic function. Of these infants, data on brain volume was available for 45 infants at 12-mo age. Infants whose sleep duration decreased less during the first year of life relative to their intercept had, on average, greater white matter volume (β = .36, p = .02). Furthermore, average sleep duration across the first year of life, and sleep duration specifically at 6 and 9 months were positively associated with white matter volume. Sleep duration during the first year of life was not significantly associated with gray matter volume at 12-mo age.</p></div><div><h3>Conclusion</h3><p>Sufficient sleep duration may benefit infant white matter development – possibly by supporting myelination. The fact that sleep duration was not associated with gray matter volume is in line with preclinical studies suggesting that sleep may be crucial for the balance between synaptogenesis and synaptic pruning but not necessarily relate to a net increase in gray matter volume. Supporting sleep during periods of rapid brain development and intervening in case of sleep problems may have long-term benefits for cognitive function and mental health.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/ee/main.PMC10313911.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life sleep disruption has long lasting, sex specific effects on later development of sleep in prairie voles","authors":"Carolyn E. Jones-Tinsley ,&nbsp;Randall J. Olson ,&nbsp;Miranda Mader ,&nbsp;Peyton T. Wickham ,&nbsp;Katelyn Gutowsky ,&nbsp;Claire Wong ,&nbsp;Sung Sik Chu ,&nbsp;Noah E.P. Milman ,&nbsp;Hung Cao ,&nbsp;Miranda M. Lim","doi":"10.1016/j.nbscr.2022.100087","DOIUrl":"10.1016/j.nbscr.2022.100087","url":null,"abstract":"<div><p>In mammals, sleep duration is highest in the early postnatal period of life and is critical for shaping neural circuits that control the development of complex behaviors. The prairie vole is a wild, highly social rodent that serves as a unique model for the study of complex, species-typical social behaviors. Previous work in our laboratory has found that early life sleep disruption (ELSD) in prairie voles during a sensitive window of postnatal development leads to long lasting changes in social and cognitive behaviors as well as structural changes in excitatory and inhibitory neural circuits in the brain. However, it is currently unknown how later sleep is impacted by ELSD, both shortly after ELSD and over the long term. Therefore, the aim of this study was to describe the effects of ELSD on later life sleep, compared to sleep in normally developing prairie voles. First, we conducted tethered electroencephalogram/electromyogram (EEG/EMG) recordings in juvenile prairie voles undergoing ELSD, compared to Control conditions. Second, we conducted 24 h of home cage tethered EEG/EMG recordings in either adolescent or adult male and female prairie voles that had previously undergone ELSD or Control conditions as juveniles. We found that, as adults, male ELSD prairie voles showed persistently lower REM sleep duration and female ELSD prairie voles showed persistently higher NREM sleep duration compared to Controls, but no other sleep parameters differed. We concluded that 1) persistent effects of ELSD on sleep into adulthood may contribute to the social and cognitive deficits observed in adult voles, and 2) sleep disruption early in life can influence later sleep patterns in adulthood.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/8d/main.PMC9879777.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9104026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical periods and Autism Spectrum Disorders, a role for sleep","authors":"Elizabeth Medina,&nbsp;Sarah Peterson,&nbsp;Kaitlyn Ford,&nbsp;Kristan Singletary,&nbsp;Lucia Peixoto","doi":"10.1016/j.nbscr.2022.100088","DOIUrl":"10.1016/j.nbscr.2022.100088","url":null,"abstract":"<div><p>Brain development relies on both experience and genetically defined programs. Time windows where certain brain circuits are particularly receptive to external stimuli, resulting in heightened plasticity, are referred to as “critical periods”. Sleep is thought to be essential for normal brain development. Importantly, studies have shown that sleep enhances critical period plasticity and promotes experience-dependent synaptic pruning in the developing mammalian brain. Therefore, normal plasticity during critical periods depends on sleep. Problems falling and staying asleep occur at a higher rate in Autism Spectrum Disorder (ASD) relative to typical development. In this review, we explore the potential link between sleep, critical period plasticity, and ASD. First, we review the importance of critical period plasticity in typical development and the role of sleep in this process. Next, we summarize the evidence linking ASD with deficits in synaptic plasticity in rodent models of high-confidence ASD gene candidates. We then show that the high-confidence rodent models of ASD that show sleep deficits also display plasticity deficits. Given how important sleep is for critical period plasticity, it is essential to understand the connections between synaptic plasticity, sleep, and brain development in ASD. However, studies investigating sleep or plasticity during critical periods in ASD mouse models are lacking. Therefore, we highlight an urgent need to consider developmental trajectory in studies of sleep and plasticity in neurodevelopmental disorders.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/3c/main.PMC9826922.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10219170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleiotropic effects of a high confidence Autism Spectrum Disorder gene, arid1b, on zebrafish sleep","authors":"Fusun Doldur-Balli ,&nbsp;Amber J. Zimmerman ,&nbsp;Brendan T. Keenan ,&nbsp;Zoe Y. Shetty ,&nbsp;Struan F.A. Grant ,&nbsp;Christoph Seiler ,&nbsp;Olivia J. Veatch ,&nbsp;Allan I. Pack","doi":"10.1016/j.nbscr.2023.100096","DOIUrl":"https://doi.org/10.1016/j.nbscr.2023.100096","url":null,"abstract":"<div><p>Sleep fulfills critical functions in neurodevelopment, such as promoting synaptic plasticity, neuronal wiring, and brain connectivity which are critical phenomena in Autism Spectrum Disorder (ASD) pathophysiology. Sleep disturbance, specifically insomnia, accompanies ASD and is associated with more severe core symptoms (e.g., social impairment). It is possible that focusing on identifying effective ways to treat sleep problems can help alleviate other ASD-related symptoms. A body of evidence indicates shared mechanisms and neurobiological substrates between sleep and ASD and investigation of these may inform therapeutic effects of improving sleep at both behavioral and molecular levels. In this study, we tested if sleep and social behavior were different in a zebrafish model with the <em>arid1b</em> gene mutated compared to controls. This gene was selected for study as expert curations conducted for the Simons Foundation for Autism Research Institute (SFARI) Gene database define it is as a ‘high confidence’ ASD gene (i.e., clearly implicated) encoding a chromatin remodeling protein. Homozygous <em>arid1b</em> mutants displayed increased arousability and light sleep compared to their heterozygous and wild type counterparts, based on testing a mechano-acoustic stimulus presenting different vibration frequencies of increasing intensity to detect sleep depth. In addition, decreased social preference was observed in <em>arid1b</em> heterozygous and homozygous mutant zebrafish. The behavioral phenotypes reported in our study are in line with findings from mouse models and human studies and demonstrate the utility of zebrafish as a vertebrate model system with high throughput phenotyping in the investigation of changes in sleep in models relevant to ASD. Furthermore, we demonstrate the importance of including assessments of arousal threshold when studying sleep using <em>in vivo</em> models.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"14 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50172770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}