ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 215 citations in OpenAlex.
- Sleep Disorders and Nonalcoholic Fatty Liver Disease: Evidence From Meta-Analysis and Mendelian Randomization.Journal of prevention (2022) · 2026Pooled it
- Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026Review
- Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders.Nature reviews. Endocrinology · 2026Review
- The G protein-coupled estrogen receptor in the nucleus accumbens mediates the estrogen-induced increase in cataplexy-like behavior.Scientific reports · 2026Article
- Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons.Nature communications · 2026Article
- Animal Models of Narcolepsy: From Orexin Deficiency to Immune Mechanisms and Regenerative Therapies.Current issues in molecular biology · 2025Review
- Probability estimation of narcolepsy type 1 in DTA mice using unlabeled EEG and EMG data.Sleep advances : a journal of the Sleep Research Society · 2025Article
- Ofatumumab treatment in new-onset narcolepsy type 1 following SARS-CoV-2 infection.Annals of clinical and translational neurology · 2025Article
- Neuropeptidergic Input from the Lateral Hypothalamus to the Suprachiasmatic Nucleus Alters the Circadian Period in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus.Experimental neurology · 2025Article
- The role of orexin and MCH neurons in the hypothalamus in sleep-wake regulation and learning-forgetting balance.Frontiers in neuroscience · 2025Review
- Functional Brain Activity Alterations in Type 1 Narcolepsy Patients with Anxiety and Depression: A 7-Tesla Resting State-Functional Magnetic Resonance Imaging Study.Nature and science of sleep · 2025Article
- Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- The Role of T Cells in the Pathogenesis of Narcolepsy Type 1: A Narrative Review.International journal of molecular sciences · 2024Review
- TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models.Scientific reports · 2024Article
- Orexin neurons play contrasting roles in itch and pain neural processing via projecting to the periaqueductal gray.Communications biology · 2024Article
- The immunopathogenesis of narcolepsy type 1.Nature reviews. Immunology · 2024Review
- Eurycoma longifolia (Tongkat Ali) supplementation enhances sleep and wake consolidation in wild-type, but not in narcoleptic mice.Sleep advances : a journal of the Sleep Research Society · 2024Article
- Hypothalamic MCH Neurons: From Feeding to Cognitive Control.Function (Oxford, England) · 2024Review
- Prostaglandin EThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
The sleep disorder narcolepsy results from loss of hypothalamic orexin/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin/hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control of the Tet-off system. Upon doxycycline removal from the diet of postpubertal orexin-tTA;TetO DTA mice, orexin neurodegeneration was rapid, with 80% cell loss within 7 d, and resulted in disrupted sleep architecture. Cataplexy, the pathognomic symptom of narcolepsy, occurred by 14 d when ∼5% of the orexin neurons remained. Cataplexy frequency increased for at least 11 weeks after doxycycline. Temporary doxycycline removal followed by reintroduction after several days enabled partial lesion of orexin neurons. DTA-induced orexin neurodegeneration caused a body weight increase without a change in food consumption, mimicking metabolic aspects of human narcolepsy. Because the orexin/hypocretin system has been implicated in the control of metabolism and addiction as well as sleep/wake regulation, orexin-tTA; TetO DTA mice are a novel model in which to study these functions, for pharmacological studies of cataplexy, and to study network reorganization as orexin input is lost.
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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.