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Cited by 301Sleep and Wakefulness ResearchNeuroscience of respiration and sleepSleep and related disorders

Concomitant loss of dynorphin, NARP, and orexin in narcolepsy

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Crocker, A., España, R. A., Papadopoulou, M., Saper, C. B., Faraco, J., Sakurai, T., Honda, M., Mignot, E. +1 more·2005·Neurology
DOI 10.1212/01.wnl.0000168173.71940.abPMC PMC2254145
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Abstract

BACKGROUND: Narcolepsy with cataplexy is associated with a loss of orexin/hypocretin. It is speculated that an autoimmune process kills the orexin-producing neurons, but these cells may survive yet fail to produce orexin. OBJECTIVE: To examine whether other markers of the orexin neurons are lost in narcolepsy with cataplexy. METHODS: We used immunohistochemistry and in situ hybridization to examine the expression of orexin, neuronal activity-regulated pentraxin (NARP), and prodynorphin in hypothalami from five control and two narcoleptic individuals. RESULTS: In the control hypothalami, at least 80% of the orexin-producing neurons also contained prodynorphin mRNA and NARP. In the patients with narcolepsy, the number of cells producing these markers was reduced to about 5 to 10% of normal. CONCLUSIONS: Narcolepsy with cataplexy is likely caused by a loss of the orexin-producing neurons. In addition, loss of dynorphin and neuronal activity-regulated pentraxin may contribute to the symptoms of narcolepsy.

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  • Selective loss of hypocretin-producing neurons causes sleepiness and cataplexy in over 90% of patients with narcolepsy.

    “Selective loss of the hypocretin-producing neurons causes sleepiness and cataplexy in over 90% of patients with narcolepsy,5–9”

    From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [9]

    The Conclusions (page unavailable) say that narcolepsy with cataplexy is likely caused by loss of orexin-producing neurons, and the Discussion links disrupted orexin signaling to sleepiness and cataplexy. The paper does not establish that this occurs in over 90% of patients: its Results report roughly 90% or greater neuron loss in two people with narcolepsy and cataplexy, not a percentage of patients. (LLM, conf=0.87)

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Research works printed but not linked: 26

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Cited by

Sorted by citations

Authors
Crocker, A., España, R. A., Papadopoulou, M., Saper, C. B., Faraco, J., Sakurai, T., Honda, M., Mignot, E., & Scammell, T. E.
Affiliations
  • Beth Israel Deaconess Medical Center (US)
  • From the Department of Neurology (A. Crocker and M. Papadopoulou, and Drs. España, Saper, and Scammell), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Psychiatry (Drs. Faraco, Honda, and Mignot), Stanford University Center for Narcolepsy, Palo Alto, CA; and Department of Pharmacology (Dr. Sakurai), Institute of Basic Medical Sciences, University of Tsukuba, Japan.
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2005-10-25
Volume
65
Issue
8
Pages
1184-1188
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/01.wnl.0000168173.71940.ab
PMC
PMC2254145
OpenAlex
W2061886084
Cited by
301
References
0
Citations by year
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FWCI
8.94
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (MH 62589, R01MH062589)
  • National Institute of Neurological Disorders and Stroke (P50NS023724, NS-23724)
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 type 1, orexin, dynorphin, prodynorphin, NARP, hypothalamus, orexin neurons, neurodegeneration, autoimmune hypothesis
MeSH terms
Orexins, Pentraxins, Aged, Autoantibodies, Brain Mapping, C-Reactive Protein, Dynorphins, Humans, Hypothalamus, Immunohistochemistry, Male, Middle Aged, Narcolepsy, Nerve Degeneration, Nerve Tissue Proteins, Neural Pathways, Neurons, Neuropeptides, RNA, Messenger, Neurodegenerative Diseases, Autoimmune Diseases of the Nervous System, Intracellular Signaling Peptides and Proteins

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