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Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons.

Overview

Authors: Thomas C Thannickal1,2, Ming-Fung Wu1,2, Marcia E Cornford3, Jerome M Siegel1,2
ORCID iDs: Thomas C Thannickal, Ming-Fung Wu, Jerome M Siegel
  1. Neuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA USA
  2. Neurobiology Research, Veterans Administration Greater Los Angeles Healthcare System, North Hills, CA USA
  3. Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA USA
Institutions: University of California, Los Angeles (United States); VA Greater Los Angeles Healthcare System (United States); Harbor–UCLA Medical Center (United States)
Journal: Nature communications, volume 17, issue 1, article 4978
Dates: received 14 April 2025; accepted 23 February 2026; published online 28 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-70899-x · PMID 41904178 · PMCID PMC13237025 · OpenAlex W7142419659
Open access: gold, a free copy (OpenAlex)
Status: data only (how the code is found and verified)
Categories: human (organism), sleep disorders (population), cellular / molecular (subfield)
Methods: Statistics, Connectivity
Keywords: Sleep disorders, Cellular neuroscience
MeSH: Locus Coeruleus*, Narcolepsy*, Neurons*, Orexins*, Adrenergic Neurons, Adult, Cataplexy, Female, Humans, Hypothalamus, Intracellular Signaling Peptides and Proteins, Male, Microglia, Middle Aged, Neuropeptides (* major topic)
Topic: Sleep and Wakefulness Research (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Citations: cited by 2 papers (Europe PMC); 84 references in the paper

Abstract

Earlier studies led to the conclusion that human narcolepsy with cataplexy was correlated with the loss of hypocretin (Hcrt = orexin) neurons in the hypothalamus. We now report that individuals having narcolepsy with cataplexy also have an average 46% loss in the number and an 18% increase in the size of brainstem norepinephrine neurons in the locus coeruleus (LC), based on our analysis of 11 brains of individuals having narcolepsy with cataplexy. Microglial clustering around Hcrt neurons in the hypothalamus and around noradrenergic neurons in the locus coeruleus of individuals having narcolepsy with cataplexy indicates microglial involvement in the degeneration of both of these neuronal groups.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data availability

All data are provided in the Source Data file groups https://figshare.com/account/items/31214965. Data is available upon request to the corresponding author after publication.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 2 keywords, 15 MeSH terms, 78 references.

Cite

This paper

Thannickal, T. C., Wu, M.-F., Cornford, M. E., & Siegel, J. M. (2026). Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons. Nature communications, 17(1), 4978. https://doi.org/10.1038/s41467-026-70899-x

BibTeX

@article{thannickal2026human,
author = {Thannickal, Thomas C and Wu, Ming-Fung and Cornford, Marcia E and Siegel, Jerome M},
title = {{Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons}},
journal = {Nature communications},
year = {2026},
month = mar,
volume = {17},
number = {1},
pages = {4978},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-70899-x},
url = {https://doi.org/10.1038/s41467-026-70899-x},
pmid = {41904178},
pmcid = {PMC13237025}
}

RIS

TY - JOUR
AU - Thannickal, Thomas C
AU - Wu, Ming-Fung
AU - Cornford, Marcia E
AU - Siegel, Jerome M
TI - Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/03/28
VL - 17
IS - 1
SP - 4978
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-70899-x
UR - https://doi.org/10.1038/s41467-026-70899-x
LA - en
ER -

CSL-JSON

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