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Cited by 167Sleep and Wakefulness ResearchNeuroscience of respiration and sleepRegulation of Appetite and Obesity

Narp immunostaining of human hypocretin (orexin) neurons: Loss in narcolepsy

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Blouin, A. M., Thannickal, T. C., Worley, P. F., Baraban, J. M., Reti, I. M., Siegel, J. M.·2005·Neurology
DOI 10.1212/01.wnl.0000175219.01544.c8PMC PMC8765220
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Abstract

OBJECTIVE: To investigate whether neuronal activity-regulated pentraxin (Narp) colocalizes with hypocretin (Hcrt or orexin) in the normal human brain and to determine if Narp staining is lost in the narcoleptic human brain. BACKGROUND: Human narcolepsy is characterized by a loss of the peptide hypocretin in the hypothalamus. This loss could result from the degeneration of neurons containing hypocretin or from a more specific loss of the ability of these neurons to synthesize Hcrt. Narp has been found to colocalize with hypocretin in the rat hypothalamus. METHODS: We investigated the distribution of Narp in three normal and four narcoleptic human postmortem brains using immunohistochemistry with an antibody to Narp. Colocalization studies of Narp and hypocretin were also performed in two normal brains using immunohistochemistry with an antibody to Narp and an antibody to hypocretin. RESULTS: We found that Narp colocalizes with hypocretin in the lateral hypothalamic area (LHA), the dorsomedial hypothalamus (DMH), the dorsal hypothalamic area (DHA), and the posterior hypothalamic area (PHA) of the normal human. The number of Narp-positive neurons was reduced by 89% in these areas of the narcoleptic hypothalamus. In contrast, Narp staining in the paraventricular (Pa) and supraoptic nuclei (SO) of the human hypothalamus did not differ between normal and narcoleptic brains. CONCLUSIONS: This finding supports the hypothesis that narcolepsy results from the specific loss of hypocretin neurons. Loss of hypothalamic Narp may contribute to the symptoms of narcolepsy.

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  • Without orexin or with altered orexin receptors, humans and animals experience narcolepsy.

    “Without orexin or with altered orexin receptors, humans and animals experience narcolepsy,34–39”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [34]

    The Background and Discussion (page not given) link human narcolepsy to loss of hypocretin (orexin) and its neurons. The paper does not report narcolepsy in animals caused by orexin loss or altered orexin receptors, so those parts of the claim are not supported by this source. (LLM, conf=0.87)

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  • Orexin neurons are both necessary and sufficient for wakefulness.

    “Orexin neurons are both necessary and sufficient for wakefulness.”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [34]

    The Abstract links narcolepsy, which involves excessive daytime sleepiness and sleep attacks, to loss of hypocretin (orexin) neurons. The Discussion concludes that these neurons are lost in narcolepsy. This supports a role in normal sleep–wake regulation, but does not establish that the neurons are either strictly necessary or sufficient for wakefulness. (LLM, conf=0.85)

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Research works printed but not linked: 9

  1. [1]Thannickal TC, Moore RY, Nienhuis R, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000;27:469–474. [DOI] [PMC free article] [PubMed] [Google Scholar]
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Sorted by citations

Authors
Blouin, A. M., Thannickal, T. C., Worley, P. F., Baraban, J. M., Reti, I. M., & Siegel, J. M.
Affiliations
Johns Hopkins University (US)
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2005-10-25
Volume
65
Issue
8
Pages
1189-1192
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/01.wnl.0000175219.01544.c8
PMC
PMC8765220
OpenAlex
W2030167280
Cited by
167
References
0
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 10 · 2014: 9 · 2013: 8 · 2012: 11
FWCI
6.62
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • National Multiple Sclerosis Society
  • VA Greater Los Angeles Healthcare System
  • National Heart, Lung, and Blood Institute (R01HL041370, R37HL041370, HL 41370)
  • National Institute of Mental Health (R01MH064109, MH 64109)
  • National Institute of Neurological Disorders and Stroke (NS 14610, R01NS014610, R37NS014610)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
NARP, orexin, narcolepsy, hypothalamus, hypocretin neurons, neuronal loss, lateral hypothalamus, dorsomedial hypothalamus, posterior hypothalamus, postmortem brain
MeSH terms
Orexins, Pentraxins, Brain Mapping, C-Reactive Protein, Humans, Hypothalamic Area, Lateral, Hypothalamus, Hypothalamus, Posterior, Immunohistochemistry, Narcolepsy, Nerve Tissue Proteins, Neural Pathways, Neurons, Neuropeptides, Sleep, Neurodegenerative Diseases, Intracellular Signaling Peptides and Proteins

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