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

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.

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Publication Details

Journal
Nature Communications
Published
2026-03-28
DOI
https://doi.org/10.1038/s41467-026-70899-x
Primary Topic
Sleep and Wakefulness Research
Type
article
Field-Weighted Citation Impact
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article

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

Thomas C. Thannickal, Marcia E. Cornford, Jerome M. Siegel, Ming-Fung Wu
Nature Communications
Sleep and Wakefulness Research
article

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

Thomas C. Thannickal, Marcia E. Cornford, Jerome M. Siegel, Ming-Fung Wu
article en

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.

Nature Communications
University of California, Los Angeles (US), UCLA Medical Center (US), Neuropsychiatric Research Institute (US), VA Greater Los Angeles Healthcare System (US), Harbor–UCLA Medical Center (US)
Openalex Percentile: Top 6%
Sleep and Wakefulness Research
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