Neurobiology of Sleep and Circadian Rhythms最新文献

{"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}

{"title":"Human circadian rhythm studies: Practical guidelines for inclusion/exclusion criteria and protocol","authors":"Yashar Yousefzadehfard ,&nbsp;Bennett Wechsler ,&nbsp;Christine DeLorenzo","doi":"10.1016/j.nbscr.2022.100080","DOIUrl":"10.1016/j.nbscr.2022.100080","url":null,"abstract":"<div><p>As interest in circadian rhythms and their effects continues to grow, there is an increasing need to perform circadian studies in humans. Although the constant routine is the gold standard for these studies, there are advantages to performing more naturalistic studies. Here, a review of protocols for such studies is provided along with sample inclusion and exclusion criteria. Sleep routines, drug use, shift work, and menstrual cycle are addressed as screening considerations. Regarding protocol, best practices for measuring melatonin, including light settings, posture, exercise, and dietary habits are described. The inclusion/exclusion recommendations and protocol guidelines are intended to reduce confounding variables in studies that do not involve the constant routine. Given practical limitations, a range of recommendations is provided from stringent to lenient. The scientific rationale behind these recommendations is discussed. However, where the science is equivocal, recommendations are based on empirical decisions made in previous studies. While not all of the recommendations listed may be practical in all research settings and with limited potential participants, the goal is to allow investigators to make well informed decisions about their screening procedures and protocol techniques and to improve rigor and reproducibility, in line with the objectives of the National Institutes of Health.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"13 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9382328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40430954","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":"Endogenous opioid signaling in the retina modulates sleep/wake activity in mice","authors":"Casey-Tyler Berezin ,&nbsp;Nikolas Bergum ,&nbsp;Kes A. Luchini ,&nbsp;Sierra Curdts ,&nbsp;Christian Korkis ,&nbsp;Jozsef Vigh","doi":"10.1016/j.nbscr.2022.100078","DOIUrl":"10.1016/j.nbscr.2022.100078","url":null,"abstract":"<div><p>Circadian sleep/wake rhythms are synchronized to environmental light/dark cycles in a process known as photoentrainment. We have previously shown that activation of β-endorphin-preferring μ-opioid receptors (MORs) inhibits the light-evoked firing of intrinsically photosensitive retinal ganglion cells (ipRGCs), the sole conduits of photoentrainment. Although we have shown that β-endorphin is expressed in the adult mouse retina, the conditions under which β-endorphin is expressed are unknown. Moreover, it is unclear whether endogenous activation of the MORs expressed by ipRGCs modulates the photoentrainment of sleep/wake cycles. To elucidate this, we first measured the mRNA expression of β-endorphin's precursor, proopiomelanocortin (POMC), at various times of day by quantitative reverse-transcription PCR. <em>POMC</em> mRNA appears to have cyclic expression in the mouse retina. We then studied β-endorphin expression with immunohistochemistry and found that retinal β-endorphin is more highly expressed in the dark/at night. Finally, we used telemetry to measure activity, EEG and EMG in freely moving animals to compare sleep/wake cycles in wild-type and transgenic mice in which only ipRGCs lack functional MORs. Results from these experiments suggest that the MORs expressed by ipRGCs contribute to the induction and maintenance of activity in the dark phase in nocturnal mice, via the promotion of wakefulness and inhibition of slow-wave sleep. Together, these data suggest that endogenous β-endorphin activates MORs expressed by ipRGCs to modulate sleep/wake activity via the photoentrainment pathway.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"13 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/1f/main.PMC9254600.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831631","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":"Sex differences in the diathetic effects of shift work schedules on circulating cytokine levels and pathological outcomes of ischemic stroke during middle age","authors":"David J. Earnest ,&nbsp;Shaina Burns ,&nbsp;Sivani Pandey ,&nbsp;Kathiresh Kumar Mani ,&nbsp;Farida Sohrabji","doi":"10.1016/j.nbscr.2022.100079","DOIUrl":"10.1016/j.nbscr.2022.100079","url":null,"abstract":"<div><p>Shift work is associated with increased risk for vascular disease, including stroke- and cardiovascular-related mortality. However, evidence from these studies is inadequate to distinguish the effect of altered circadian rhythms in isolation from other risk factors for stroke associated with shift work (e.g., smoking, poor diet, lower socioeconomic status). Thus, the present study examined the diathetic effects of exposure to shifted LD cycles during early adulthood on circadian rhythmicity, inflammatory signaling and ischemic stroke pathology during middle age, when stroke risk is high and outcomes are more severe. Entrainment of circadian activity was stable in all animals maintained on a fixed light:dark 12:12 cycle but was severely disrupted during exposure to shifted LD cycles (12hr advance/5d). Following treatment, circadian entrainment in the shifted LD group was distinguished by increased daytime activity and decreased rhythm amplitude that persisted into middle-age. Circadian rhythm desynchronization in shifted LD males and females was accompanied by significant elevations in circulating levels of the inflammatory cytokine IL-17A and gut-derived inflammatory mediator lipopolysaccharide (LPS) during the post-treatment period. Middle-cerebral artery occlusion, 3 months after exposure to shifted LD cycles, resulted in greater post-stroke mortality in shifted LD females. In surviving subjects, sensorimotor performance, assessed 2- and 5-days post-stroke, was impaired in males of both treatment groups, whereas in females, recovery of function was observed in fixed but not shifted LD rats. Overall, these results indicate that early exposure to shifted LD cycles promotes an inflammatory phenotype that amplifies stroke impairments, specifically in females, later in life.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"13 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/c6/main.PMC9253906.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40481108","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}