ArticleSleep2016
Progressive Loss of the Orexin Neurons Reveals Dual Effects on Wakefulness.
Article in Sleep, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Number, Duration, and Distribution of Wake Bouts in Patients with Insomnia Disorder: Effect of Daridorexant and Zolpidem.CNS drugs · 2023Trial
- Orexin-A and Circadian Disruption in Alzheimer's Disease: Implications for Amyloid-Beta Pathology.Molecular neurobiology · 2025Article
- The interaction between orexin, sleep deprivation and Alzheimer's disease: Unveiling an Emerging Connection.The journal of physiological sciences : JPS · 2025Review
- The role of orexin and MCH neurons in the hypothalamus in sleep-wake regulation and learning-forgetting balance.Frontiers in neuroscience · 2025Review
- Hypocretin: a promising target for the regulation of homeostasis.Frontiers in neuroscience · 2025Review
- Structure and Function of Neuronal Circuits Linking Ventrolateral Preoptic Nucleus and Lateral Hypothalamic Area.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations.Nature and science of sleep · 2023Review
- Orexin neurons inhibit sleep to promote arousal.Nature communications · 2022Article
- Current Understanding of Narcolepsy 1 and its Comorbidities: What Clinicians Need to Know.Advances in therapy · 2022Review
- What evidence is there for implicating the brain orexin system in neuropsychiatric symptoms in dementia?Frontiers in psychiatry · 2022Article
- Disrupted nighttime sleep and sleep instability in narcolepsy.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2022Review
- Tau-driven degeneration of sleep- and wake-regulating neurons in Alzheimer's disease.Sleep medicine reviews · 2021Review
- Stability of nocturnal wake and sleep stages defines central nervous system disorders of hypersomnolence.Sleep · 2021Article
- Large-scale functional brain networks for consciousness.Anatomy & cell biology · 2021Review
- Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2021Article
- The Impacts of Age and Sex in a Mouse Model of Childhood Narcolepsy.Frontiers in neuroscience · 2021Article
- Light/Clock Influences Membrane Potential Dynamics to Regulate Sleep States.Frontiers in neurology · 2021Review
- Defining disrupted nighttime sleep and assessing its diagnostic utility for pediatric narcolepsy type 1.Sleep · 2020Article
- Article
- The neurobiological basis of narcolepsy.Nature reviews. Neuroscience · 2019Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STUDY
objectivesNarcolepsy is caused by loss of the orexin (also known as hypocretin) neurons. In addition to the orexin peptides, these neurons release additional neurotransmitters, which may produce complex effects on sleep/wake behavior. Currently, it remains unknown whether the orexin neurons promote the initiation as well as the maintenance of wakefulness, and whether the orexin neurons influence initiation or maintenance of sleep. To determine the effects of the orexin neurons on the dynamics of sleep/wake behavior, we analyzed sleep/wake architecture in a novel mouse model of acute orexin neuron loss.
methodsWe used survival analysis and other statistical methods to analyze sleep/wake architecture in orexin-tTA ; TetO diphtheria toxin A mice at different stages of orexin neuron degeneration.
resultsProgressive loss of the orexin neurons dramatically reduced survival of long wake bouts, but it also improved survival of brief wake bouts. In addition, with loss of the orexin neurons, mice were more likely to wake during the first 30 sec of nonrapid eye movement sleep and then less likely to return to sleep during the first 60 sec of wakefulness.
conclusionsThese findings help explain the sleepiness and fragmented sleep that are characteristic of narcolepsy. Orexin neuron loss impairs survival of long wake bouts resulting in poor maintenance of wakefulness, but this neuronal loss also fragments sleep by increasing the risk of awakening at the beginning of sleep and then reducing the likelihood of quickly returning to sleep.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.