ArticleThe Journal of clinical investigation2014
Orexin neurons suppress narcolepsy via 2 distinct efferent pathways.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 164 citations in OpenAlex.
- Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders.Nature reviews. Endocrinology · 2026Review
- Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Propofol regulates arousal by enhancing inhibitory synaptic transmission of noradrenergic neurons in the locus coeruleus of adult male mice.Scientific reports · 2025Article
- Hypothalamic Orexin Projections to the Hippocampal CA1 Region Alleviate Cognitive and Synaptic Plasticity Impairments Induced by Blue Light Exposure.CNS neuroscience & therapeutics · 2025Article
- Narcolepsy and rapid eye movement sleep.Journal of sleep research · 2025Review
- A neural circuit associated with anxiety-like behaviors induced by chronic inflammatory pain and the anxiolytic effects of electroacupuncture.CNS neuroscience & therapeutics · 2024Article
- The Orexin/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress.Biomedicines · 2024Review
- Inactivation of hypocretin receptor-2 signaling in dopaminergic neurons induces hyperarousal and enhanced cognition but impaired inhibitory control.Molecular psychiatry · 2024Article
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- A molecular network map of orexin-orexin receptor signaling system.Journal of cell communication and signaling · 2023Article
- Amygdala neurocircuitry at the interface between emotional regulation and narcolepsy with cataplexy.Frontiers in neuroscience · 2023Review
- Progress of autonomic disturbances in narcolepsy type 1.Frontiers in neurology · 2023Review
- Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations.Nature and science of sleep · 2023Review
- Orexin, Sleep, Sympathetic Neural Activity, and Cardiovascular Function.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Paraventricular hypothalamic vasopressin neurons induce self-grooming in mice.Molecular brain · 2022Article
- Activity of putative orexin neurons during cataplexy.Molecular brain · 2022Article
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- Identification and Characterization of Cannabidiol as an OX1R Antagonist by Computational and In Vitro Functional Validation.Biomolecules · 2021Article
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12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The loss of orexin neurons in humans is associated with the sleep disorder narcolepsy, which is characterized by excessive daytime sleepiness and cataplexy. Mice lacking orexin peptides, orexin neurons, or orexin receptors recapitulate human narcolepsy phenotypes, further highlighting a critical role for orexin signaling in the maintenance of wakefulness. Despite the known role of orexin neurons in narcolepsy, the precise neural mechanisms downstream of these neurons remain unknown. We found that targeted restoration of orexin receptor expression in the dorsal raphe (DR) and in the locus coeruleus (LC) of mice lacking orexin receptors inhibited cataplexy-like episodes and pathological fragmentation of wakefulness (i.e., sleepiness), respectively. The suppression of cataplexy-like episodes correlated with the number of serotonergic neurons restored with orexin receptor expression in the DR, while the consolidation of fragmented wakefulness correlated with the number of noradrenergic neurons restored in the LC. Furthermore, pharmacogenetic activation of these neurons using designer receptor exclusively activated by designer drug (DREADD) technology ameliorated narcolepsy in mice lacking orexin neurons. These results suggest that DR serotonergic and LC noradrenergic neurons play differential roles in orexin neuron-dependent regulation of sleep/wakefulness and highlight a pharmacogenetic approach for the amelioration of narcolepsy.
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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.