Neurobiology of Sleep and Circadian Rhythms最新文献

{"title":"Habitual sleep durations and subjective sleep quality predict white matter differences in the human brain","authors":"Sakh Khalsa ,&nbsp;Joanne R. Hale ,&nbsp;Aimee Goldstone ,&nbsp;Rebecca S. Wilson ,&nbsp;Stephen D. Mayhew ,&nbsp;Manny Bagary ,&nbsp;Andrew P. Bagshaw","doi":"10.1016/j.nbscr.2017.03.001","DOIUrl":"10.1016/j.nbscr.2017.03.001","url":null,"abstract":"<div><p>Self-imposed short sleep durations are increasingly commonplace in society, and have considerable health and performance implications for individuals. Reduced sleep duration over multiple nights has similar behavioural effects to those observed following acute total sleep deprivation, suggesting that lack of sleep affects brain function cumulatively. A link between habitual sleep patterns and functional connectivity has previously been observed, and the effect of sleep duration on the brain's intrinsic functional architecture may provide a link between sleep status and cognition. However, it is currently not known whether differences in habitual sleep patterns across individuals are related to changes in the brain's white matter, which underlies structural connectivity. In the present study we use diffusion–weighted imaging and a group comparison application of tract based spatial statistics (TBSS) to investigate changes to fractional anisotropy (FA) and mean diffusivity (MD) in relation to sleep duration and quality, hypothesising that white matter metrics would be positively associated with sleep duration and quality. Diffusion weighted imaging data was acquired from a final cohort of 33 (23–29 years, 10 female, mean 25.4 years) participants. Sleep patterns were assessed for a 14<!--> <!-->day period using wrist actigraphs and sleep diaries, and subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Median splits based on total sleep time and PSQI were used to create groups of shorter/longer and poorer/better sleepers, whose imaging data was compared using TBSS followed by post-hoc correlation analysis in regions identified as significantly different between the groups<strong>.</strong> There were significant positive correlations between sleep duration and FA in the left orbito-frontal region and the right superior corona radiata, and significant negative correlations between sleep duration and MD in right orbito-frontal white matter and the right inferior longitudinal fasciculus. Improved sleep quality was positively correlated with FA in left caudate nucleus, white matter tracts to the left orbito-frontal region, the left anterior cingulum bundle and the white matter tracts associated with the right operculum and insula, and negatively correlated with MD in left orbito-frontal white matter and the left anterior cingulum bundle. Our findings suggest that reduced cumulative total sleep time (cTST) and poorer subjective sleep quality are associated with subtle white matter micro-architectural changes. The regions we identified as being related to habitual sleep patterns were restricted to the frontal and temporal lobes, and the functions they support are consistent with those which have previously been demonstrated as being affected by short sleep durations (e.g., attention, cognitive control, memory). Examining how inter-individual differences in brain structure are related to habitual sleep patterns could help to she","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2017.03.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37359400","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":"Interleukin 37 expression in mice alters sleep responses to inflammatory agents and influenza virus infection","authors":"Christopher J. Davis ,&nbsp;Mark R. Zielinski ,&nbsp;Danielle Dunbrasky ,&nbsp;Ping Taishi ,&nbsp;Charles A. Dinarello ,&nbsp;James M. Krueger","doi":"10.1016/j.nbscr.2016.11.005","DOIUrl":"10.1016/j.nbscr.2016.11.005","url":null,"abstract":"<div><p>Multiple interactions between the immune system and sleep are known, including the effects of microbial challenge on sleep or the effects of sleep loss on facets of the immune response. Cytokines regulate, in part, sleep and immune responses. Here we examine the role of an anti-inflammatory cytokine, interleukin-37 (IL-37) on sleep in a mouse strain that expresses human IL-37b (<em>IL37</em>tg mice). Constitutive expression of the <em>IL-37</em> gene in the brains of these mice under resting conditions is low; however, upon an inflammatory stimulus, expression increases dramatically. We measured sleep in three conditions; (a) under baseline conditions and after 6<!--> <!-->h of sleep loss, (b) after bolus intraperitoneal administration of lipopolysaccharide (LPS) or IL-1β and (c) after intranasal influenza virus challenge. Under baseline conditions, the <em>IL37</em>tg mice had 7% more spontaneous non-rapid eye movement sleep (NREMS) during the light period than wild-type (WT) mice. After sleep deprivation both WT mice and <em>IL37</em>tg mice slept an extra 21% and 12%, respectively, during the first 6<!--> <!-->h of recovery. NREMS responses after sleep deprivation did not significantly differ between WT mice and <em>IL37</em>tg mice. However, in response to either IL-1β or LPS, the increases in time spent in NREMS were about four-fold greater in the WT mice than in the <em>IL37</em>tg mice. In contrast, in response to a low dose of mouse-adapted H1N1 influenza virus, sleep responses developed slowly over the 6<!--> <!-->day recording period. By day 6, NREMS increased by 10% and REMS increased by 18% in the <em>IL37</em>tg mice compared to the WT mice. Further, by day 4 <em>IL37</em>tg mice lost less weight, remained more active, and retained their body temperatures closer to baseline values than WT mice. We conclude that conditions that promote IL-37 expression attenuate morbidity to severe inflammatory challenge.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.11.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54917555","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 in Alzheimer's Disease–Beyond Amyloid","authors":"Jerrah K. Holth,&nbsp;Tirth K. Patel,&nbsp;David M. Holtzman","doi":"10.1016/j.nbscr.2016.08.002","DOIUrl":"10.1016/j.nbscr.2016.08.002","url":null,"abstract":"<div><p>Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well established with disturbed sleep and increased wakefulness leading to increased Aβ production and decreased Aβ clearance; whereas Aβ deposition is associated with increased wakefulness and sleep disturbances. Aβ fluctuates with the sleep-wake cycle and is higher during wakefulness and lower during sleep. This fluctuation is lost with Aβ deposition, likely due to its sequestration into amyloid plaques. As such, Aβ is believed to play a significant role in the development of sleep disturbances in the preclinical and clinical phases of AD. In addition to Aβ, the influence of tau AD pathology is likely important to the sleep disturbances observed in AD. Abnormal tau is the earliest observable AD-like pathology in the brain with abnormal tau phosphorylation in many sleep regulating regions such as the locus coeruleus, dorsal raphe, tuberomammillary nucleus, parabrachial nucleus, and basal forebrain prior to the appearance of amyloid or cortical tau pathology. Furthermore, human tau mouse models exhibit AD-like sleep disturbances and sleep changes are common in other tauopathies including frontotemporal dementia and progressive supranuclear palsy. Together these observations suggest that tau pathology can induce sleep disturbances and may play a large role in the sleep disruption seen in AD. To elucidate the relationship between sleep and AD it will be necessary to not only understand the role of amyloid but also tau and how these two pathologies, together with comorbid pathology such as alpha-synuclein, interact and affect sleep regulation in the brain.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54917455","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":"The role of sleep in recovery following ischemic stroke: A review of human and animal data","authors":"Simone B. Duss ,&nbsp;Andrea Seiler ,&nbsp;Markus H. Schmidt ,&nbsp;Marta Pace ,&nbsp;Antoine Adamantidis ,&nbsp;René M. Müri ,&nbsp;Claudio L. Bassetti","doi":"10.1016/j.nbscr.2016.11.003","DOIUrl":"10.1016/j.nbscr.2016.11.003","url":null,"abstract":"<div><p>Despite advancements in understanding the pathophysiology of stroke and the state of the art in acute management of afflicted patients as well as in subsequent neurorehabilitation training, stroke remains the most common neurological cause of long-term disability in adulthood. To enhance stroke patients’ independence and well-being it is necessary, therefore, to consider and develop new therapeutic strategies and approaches. We postulate that sleep might play a pivotal role in neurorehabilitation following stroke. Over the last two decades compelling evidence for a major function of sleep in neuroplasticity and neural network reorganization underlying learning and memory has evolved. Training and learning of new motor skills and knowledge can modulate the characteristics of subsequent sleep, which additionally can improve memory performance. While healthy sleep appears to support neuroplasticity resulting in improved learning and memory, disturbed sleep following stroke in animals and humans can impair stroke outcome. In addition, sleep disorders such as sleep disordered breathing, insomnia, and restless legs syndrome are frequent in stroke patients and associated with worse recovery outcomes. Studies investigating the evolution of post-stroke sleep changes suggest that these changes might also reflect neural network reorganization underlying functional recovery. Experimental and clinical studies provide evidence that pharmacological sleep promotion in rodents and treatment of sleep disorders in humans improves functional outcome following stroke. Taken together, there is accumulating evidence that sleep represents a “plasticity state” in the process of recovery following ischemic stroke. However, to test the key role of sleep and sleep disorders for stroke recovery and to better understand the underlying molecular mechanisms, experimental research and large-scale prospective studies in humans are necessary. The effects of hospital conditions, such as adjusting light conditions according to the patients’ sleep-wake rhythms, or sleep promoting drugs and non-invasive brain stimulation to promote neuronal plasticity and recovery following stroke requires further investigation.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.11.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37359399","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 and clocks – implications for brain health","authors":"Erik S. Musiek,&nbsp;Aleksandar Videnovic","doi":"10.1016/j.nbscr.2016.12.001","DOIUrl":"10.1016/j.nbscr.2016.12.001","url":null,"abstract":"","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37364589","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 variability of the initial Glasgow Coma Scale score in traumatic brain injury patients","authors":"John K. Yue ,&nbsp;Caitlin K. Robinson ,&nbsp;Ethan A. Winkler ,&nbsp;Pavan S. Upadhyayula ,&nbsp;John F. Burke ,&nbsp;Romain Pirracchio ,&nbsp;Catherine G. Suen ,&nbsp;Hansen Deng ,&nbsp;Laura B. Ngwenya ,&nbsp;Sanjay S. Dhall ,&nbsp;Geoffrey T. Manley ,&nbsp;Phiroz E. Tarapore","doi":"10.1016/j.nbscr.2016.09.002","DOIUrl":"10.1016/j.nbscr.2016.09.002","url":null,"abstract":"<div><h3>Introduction</h3><p>The Glasgow Coma Scale (GCS) score is the primary method of assessing consciousness after traumatic brain injury (TBI), and the clinical standard for classifying TBI severity. There is scant literature discerning the influence of circadian rhythms or emergency department (ED) arrival hour on this important clinical tool.</p></div><div><h3>Methods</h3><p>Retrospective cohort analysis of adult patients suffering blunt TBI using the National Sample Program of the National Trauma Data Bank, years 2003–2006. ED arrival GCS score was characterized by midday (10<!--> <!-->a.m.–4<!--> <!-->p.m.) and midnight (12<!--> <!-->a.m.–6<!--> <!-->a.m.) cohorts (N=24548). Proportions and standard errors are reported for descriptive data. Multivariable regressions using odds ratios (OR), mean differences (<em>B</em>), and their associated 95% confidence intervals [CI] were performed to assess associations between ED arrival hour and GCS score. Statistical significance was assessed at p&lt;0.05.</p></div><div><h3>Results</h3><p>Patients were 42.48±0.13-years-old and 69.5% male. GCS score was 12.68±0.13 (77.2% mild, 5.2% moderate, 17.6% severe-TBI). Overall, patients were injured primarily via motor vehicle accidents (52.2%) and falls (24.2%), and 85.7% were admitted to hospital (33.5% ICU). Injury severity score did not differ between day and nighttime admissions.</p><p>Nighttime admissions associated with decreased systemic comorbidities (p&lt;0.001) and increased likelihood of alcohol abuse and drug intoxication (p&lt;0.001). GCS score demonstrated circadian rhythmicity with peak at 12<!--> <!-->p.m. (13.03±0.08) and nadir at 4am (12.12±0.12). Midnight patients demonstrated lower GCS (12<!--> <!-->a.m.–6<!--> <!-->a.m.: 12.23±0.04; 10<!--> <!-->a.m.–4<!--> <!-->p.m.: 12.95±0.03, p&lt;0.001). Multivariable regression adjusted for demographic and injury factors confirmed that midnight-hours independently associated with decreased GCS (<em>B</em>=−0.29 [−0.40, −0.19]).</p><p>In patients who did not die in ED or go directly to surgery (N=21862), midnight-hours (multivariable OR 1.73 [1.30–2.31]) associated with increased likelihood of ICU admission; increasing GCS score (per-unit OR 0.82 [0.80–0.83]) associated with decreased odds. Notably, the interaction factor ED GCS score*ED arrival hour independently demonstrated OR 0.96 [0.94–0.98], suggesting that the influence of GCS score on ICU admission odds is less important at night than during the day.</p></div><div><h3>Conclusions</h3><p>Nighttime TBI patients present with decreased GCS scores and are admitted to ICU at higher rates, yet have fewer prior comorbidities and similar systemic injuries. The interaction between nighttime hours and decreased GCS score on ICU admissions has important implications for clinical assessment/triage.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37359397","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":"Prolonged day length exposure improves circadian deficits and survival in a transgenic mouse model of Huntington's disease","authors":"Koliane Ouk,&nbsp;Juliet Aungier,&nbsp;A. Jennifer Morton","doi":"10.1016/j.nbscr.2016.11.004","DOIUrl":"10.1016/j.nbscr.2016.11.004","url":null,"abstract":"<div><p>The circadian disruption seen in patients of Huntington's disease (HD) is recapitulated in the R6/2 mouse model. As the disease progresses, the activity of R6/2 mice increases dramatically during the rest (light) period and decreases during the active (dark) period, eventually leading to a complete disintegration of rest-activity rhythms by the age of ~16 weeks. The suprachiasmatic nucleus controls circadian rhythms by entraining the rest-activity rhythms to the environmental light-dark cycle. Since R6/2 mice can shift their rest-activity rhythms in response to a jet-lag paradigm and also respond positively to bright light therapy (1000 lx), we investigated whether or not a prolonged day length exposure could reduce their daytime activity and improve their behavioural circadian rhythms. We found that a long-day photoperiod (16<!--> <!-->h light/8<!--> <!-->h dark cycle; 100 lx) significantly improved the survival of R6/2 female mice by 2.4 weeks, compared to mice kept under standard conditions (12<!--> <!-->h light/12<!--> <!-->h dark cycle). Furthermore, a long-day photoperiod improved the nocturnality of R6/2 female mice. Mice kept under long-day photoperiod also maintained acrophase in activity rhythms (a parameter of rhythmicity strength) in phase with that of WT mice, even if they were symptomatic. By contrast, a short-day photoperiod (8<!--> <!-->h light/16<!--> <!-->h dark cycle) was deleterious to R6/2 female mice and further reduced the survival by ~1 week. Together, our results support the idea that light therapy may be beneficial for improving circadian dysfunction in HD patients.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.11.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37364590","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":"EEG slow waves in traumatic brain injury: Convergent findings in mouse and man","authors":"Mo H. Modarres ,&nbsp;Nicholas N. Kuzma ,&nbsp;Tracy Kretzmer ,&nbsp;Allan I. Pack ,&nbsp;Miranda M. Lim","doi":"10.1016/j.nbscr.2016.06.001","DOIUrl":"10.1016/j.nbscr.2016.06.001","url":null,"abstract":"<div><h3>Objective</h3><p>Evidence from previous studies suggests that greater sleep pressure, in the form of EEG-based slow waves, accumulates in specific brain regions that are more active during prior waking experience. We sought to quantify the number and coherence of EEG slow waves in subjects with mild traumatic brain injury (mTBI).</p></div><div><h3>Methods</h3><p>We developed a method to automatically detect individual slow waves in each EEG channel, and validated this method using simulated EEG data. We then used this method to quantify EEG-based slow waves during sleep and wake states in both mouse and human subjects with mTBI. A modified coherence index that accounts for information from multiple channels was calculated as a measure of slow wave synchrony.</p></div><div><h3>Results</h3><p>Brain-injured mice showed significantly higher theta:alpha amplitude ratios and significantly more slow waves during spontaneous wakefulness and during prolonged sleep deprivation, compared to sham-injured control mice. Human subjects with mTBI showed significantly higher theta:beta amplitude ratios and significantly more EEG slow waves while awake compared to age-matched control subjects. We then quantified the global coherence index of slow waves across several EEG channels in human subjects. Individuals with mTBI showed significantly less EEG global coherence compared to control subjects while awake, but not during sleep. EEG global coherence was significantly correlated with severity of post-concussive symptoms (as assessed by the Neurobehavioral Symptom Inventory scale).</p></div><div><h3>Conclusion and implications</h3><p>Taken together, our data from both mouse and human studies suggest that EEG slow wave quantity and the global coherence index of slow waves may represent a sensitive marker for the diagnosis and prognosis of mTBI and post-concussive symptoms.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37364592","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 dysregulation in Parkinson's disease","authors":"Aleksandar Videnovic ,&nbsp;Diego Golombek","doi":"10.1016/j.nbscr.2016.11.001","DOIUrl":"10.1016/j.nbscr.2016.11.001","url":null,"abstract":"<div><p>Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects over one million individuals in the US alone. PD is characterized by a plethora of motor and non-motor manifestations, resulting from a progressive degeneration of dopaminergic neurons and disbalance of several other neurotransmitters. A growing body of evidence points to significant alterations of the circadian system in PD. This is not surprising given the pivotal role that dopamine plays in circadian regulation as well as the role of circadian influences in dopamine metabolism. In this review we present basic and clinical investigations that examined the function of the circadian system in PD.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35173580","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":"Hypocretinergic and cholinergic contributions to sleep-wake disturbances in a mouse model of traumatic brain injury","authors":"Hannah E. Thomasy ,&nbsp;Heidi Y. Febinger ,&nbsp;Kristyn M. Ringgold ,&nbsp;Carmelina Gemma ,&nbsp;Mark R. Opp","doi":"10.1016/j.nbscr.2016.03.001","DOIUrl":"10.1016/j.nbscr.2016.03.001","url":null,"abstract":"<div><p>Disorders of sleep and wakefulness occur in the majority of individuals who have experienced traumatic brain injury (TBI), with increased sleep need and excessive daytime sleepiness often reported. Behavioral and pharmacological therapies have limited efficacy, in part, because the etiology of post-TBI sleep disturbances is not well understood. Severity of injuries resulting from head trauma in humans is highly variable, and as a consequence so are their sequelae. Here, we use a controlled laboratory model to investigate the effects of TBI on sleep-wake behavior and on candidate neurotransmitter systems as potential mediators. We focus on hypocretin and melanin-concentrating hormone (MCH), hypothalamic neuropeptides important for regulating sleep and wakefulness, and two potential downstream effectors of hypocretin actions, histamine and acetylcholine. Adult male C57BL/6 mice (<em>n</em>=6–10/group) were implanted with EEG recording electrodes and baseline recordings were obtained. After baseline recordings, controlled cortical impact was used to induce mild or moderate TBI. EEG recordings were obtained from the same animals at 7 and 15 days post-surgery. Separate groups of animals (<em>n</em>=6–8/group) were used to determine effects of TBI on the numbers of hypocretin and MCH-producing neurons in the hypothalamus, histaminergic neurons in the tuberomammillary nucleus, and cholinergic neurons in the basal forebrain. At 15 days post-TBI, wakefulness was decreased and NREM sleep was increased during the dark period in moderately injured animals. There were no differences between groups in REM sleep time, nor were there differences between groups in sleep during the light period. TBI effects on hypocretin and cholinergic neurons were such that more severe injury resulted in fewer cells. Numbers of MCH neurons and histaminergic neurons were not altered under the conditions of this study. Thus, we conclude that moderate TBI in mice reduces wakefulness and increases NREM sleep during the dark period, effects that may be mediated by hypocretin-producing neurons and/or downstream cholinergic effectors in the basal forebrain.</p></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nbscr.2016.03.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37364593","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}