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Cited by 463Parkinson's Disease Mechanisms and TreatmentsSleep and Wakefulness ResearchNuclear Receptors and Signaling

Hypocretin (orexin) loss in Parkinson's disease

Fronczek, R., Overeem, S., Lee, S. Y. Y., Hegeman, Ingrid. M., van Pelt, J., van Duinen, Sjoerd. G., Lammers, G. J., Swaab, D. F.·2007·Brain
DOI 10.1093/brain/awm090
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Abstract

The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradictory results. In PD patients and matched controls, we (i) estimated the number of hypocretin neurons in post-mortem hypothalami using immunocytochemistry and an image analysis system (ii) quantified hypocretin levels in post-mortem ventricular CSF and (iii) prefrontal cortex using a radioimmunoassay. Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th-75th percentile). We showed a significant decrease between PD patients and controls in (i) the number of hypocretin neurons (PD: 20 276 (13 821-31 229); controls: 36 842 (32 546-50 938); P = 0.016); (ii) the hypocretin-1 concentration in post-mortem ventricular CSF (PD: 365.5 pg/ml (328.0-448.3); controls: 483.5 (433.5-512.3); P = 0.012) and (iii) the hypocretin-1 concentrations in prefrontal cortex (PD: 389.6 pg/g (249.2-652.2); controls: 676.6 (467.5-883.9); P = 0.043). Hypocretin neurotransmission is affected in PD. The hypocretin-1 concentration in the prefrontal cortex was almost 40% lower in PD patients, while ventricular CSF levels were almost 25% reduced. The total number of hypocretin neurons was almost half compared to controls.

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  • In controls, the total number of hypocretin neurons and their distribution across the lateral and posterior hypothalamus were similar to prior reports.

    “In controls, the total number of hypocretin neurons and their distribution across the lateral and posterior hypothalamus were similar to prior reports.7,8,14,15”

    From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [14]

    The Hypocretin-1 cell number section reports a control median of 36,842 neurons, and the Hypocretin-1 histochemistry section says their distribution matched an earlier description in the perifornical lateral hypothalamus. Our copy does not compare the control total with prior reports or explicitly describe a distribution across both the lateral and posterior hypothalamus. Page numbers were not available in the indexed passages. (LLM, conf=0.83)

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Authors
Fronczek, R., Overeem, S., Lee, S. Y. Y., Hegeman, I. M., van Pelt, J., van Duinen, S. G., Lammers, G. J., & Swaab, D. F.
Affiliations
Radboud University Nijmegen (NL)
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2007-04-23
Volume
130
Issue
6
Pages
1577-1585
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awm090
OpenAlex
W2143505927
Cited by
463
References
4
Citations by year
2026: 11 · 2025: 11 · 2024: 27 · 2023: 20 · 2022: 22 · 2021: 25 · 2020: 19 · 2019: 20 · 2018: 21 · 2017: 24 · 2016: 27 · 2015: 23 · 2014: 29 · 2013: 25 · 2012: 29
FWCI
19.91
Type
journal article
Language
en
Open access
closed
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
orexin, Parkinson's disease, hypocretin neurons, hypothalamus, prefrontal cortex, Lewy bodies, sleep disorders, non-motor symptoms, postmortem brain
MeSH terms
Orexins, Aged, Aged, 80 and over, Cell Count, Female, Humans, Hypothalamus, Immunoenzyme Techniques, Male, Middle Aged, Neurons, Neuropeptides, Parkinson Disease, Lewy Bodies, Prefrontal Cortex, Intracellular Signaling Peptides and Proteins

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