Cited by 289Sleep and Wakefulness ResearchNeuroscience of respiration and sleepSleep and related disorders

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The neurobiological basis of narcolepsy

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Mahoney, Carrie E., Cogswell, Andrew, Koralnik, Igor J., Scammell, Thomas E.·2019·Nature Reviews Neuroscience

DOI 10.1038/s41583-018-0097-xPMC PMC6492289

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Abstract

Narcolepsy is the most common neurological cause of chronic sleepiness. The discovery about 20 years ago that narcolepsy is caused by selective loss of the neurons producing orexins (also known as hypocretins) sparked great advances in the field. Here, we review the current understanding of how orexin neurons regulate sleep-wake behaviour and the consequences of the loss of orexin neurons. We also summarize the developing evidence that narcolepsy is an autoimmune disorder that may be caused by a T cell-mediated attack on the orexin neurons and explain how these new perspectives can inform better therapeutic approaches.

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Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor
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Orexin Neurons Are Necessary for the Circadian Control of REM Sleep
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Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity
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Role of the Medial Prefrontal Cortex in Cataplexy
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Selective expression of Narp, a secreted neuronal pentraxin, in orexin neurons
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Comprehensive Behavioral Analysis of Male Ox1r−/− Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior
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Antagonism of orexin receptors significantly lowers blood pressure in spontaneously hypertensive rats
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Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns
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Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity
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Authors: Mahoney, C. E., Cogswell, A., Koralnik, I. J., & Scammell, T. E.
Affiliations: Beth Israel Deaconess Medical Center (US)
Rush University Medical Center (US)
Corresponding author: Scammell, Thomas E.
ORCID: Mahoney, Carrie E.
Cogswell, Andrew
Koralnik, Igor J.
Scammell, Thomas E.
Venue: Nature Reviews Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2018-12-13
Volume: 20
Issue: 2
Pages: 83-93
ISSN: 1471-003X (ISSN-L)
1471-0048
DOI: 10.1038/s41583-018-0097-x
PMC: PMC6492289
OpenAlex: W2904386018
Cited by: 289
References: 209
Citations by year: 2026: 30 · 2025: 58 · 2024: 45 · 2023: 43 · 2022: 43 · 2021: 30 · 2020: 20 · 2019: 19
FWCI: 2.30
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (P01HL095491)
National Institute of Neurological Disorders and Stroke (R21NS099787, R01NS106032)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords: narcolepsy, orexin neurons, orexin, sleep-wake regulation, autoimmune disease, neurodegeneration, treatment options
MeSH terms: Orexins, Animals, Autoimmune Diseases, Humans, Narcolepsy, Nervous System, Neurobiology

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The neurobiological basis of narcolepsy

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