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Cited by 126Multiple Sclerosis Research StudiesStress Responses and CortisolAdrenal Hormones and Disorders

Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions

Huitinga, Inge, Erkut, Zeynel A., van Beurden, Denis, Swaab, Dick F.·2004·Annals of Neurology
DOI 10.1002/ana.10766
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Abstract

In this postmortem study, we investigated the relationship between multiple sclerosis (MS) lesions in the hypothalamus and the state of activity of corticotropin-releasing hormone (CRH)-producing neurons that control the hypothalamus-pituitary-adrenal (HPA) axis. A high incidence (15/16) of MS lesions was found in the hypothalamus, of which more than 50% was active, that is, contained activated macrophages. MS patients have increased numbers of CRH-immunoreactive neurons coexpressing vasopressin (CRH/VP neurons), a sign of chronic activation of CRH neurons and increased CRH mRNA expression. Active MS lesions correlated with a low number of hyperactive CRH/VP neurons. High human leukocyte antigen (HLA)-DR, -DP, -DQ expression, a measure for macrophage and microglial activation, correlated with low CRH mRNA expression. The nearer the HLA expression was situated to the CRH neurons, the stronger the inhibiting effect, suggesting that activated microglial cells or macrophages suppress these neurons. The more active MS lesions were present in the hypothalamus, the shorter was the disease duration until the moment of death, indicating an unfavorable course of the disease. Thus, MS patients have a chronically activated CRH system, but, in the subgroup of patients with active MS lesions in the hypothalamus, this activation is impaired and the disease course is worse.

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  • Neuropathological studies reported a high proportion of patients with inflammatory and demyelinating lesions of the hypothalamus, with indices of altered HPA activity.

    “Additionally, neuropathological studies reported a high proportion of patients with inflammatory and demyelinating lesions of the hypothalamus, with indices of altered HPA activity (Huitinga et al., 2001, 2004).”

    From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Huitinga et al., 2004

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Authors
Huitinga, I., Erkut, Z. A., van Beurden, D., & Swaab, D. F.
Affiliations
Royal Netherlands Academy of Arts and Sciences (NL)
Corresponding author
Huitinga, Inge
ORCID
Venue
Annals of Neurology
Publisher
Wiley
Published
2003-12
Volume
55
Issue
1
Pages
37-45
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.10766
OpenAlex
W2125763025
Cited by
126
References
33
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 5
FWCI
3.02
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
multiple sclerosis, hypothalamus, hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor, HLA class II expression, macrophage activation, microglial activation, lesion activity, disease duration, postmortem brain
MeSH terms
Adult, Aged, Aged, 80 and over, Corticotropin-Releasing Hormone, Female, HLA Antigens, Humans, Hypothalamo-Hypophyseal System, Hypothalamus, Image Processing, Computer-Assisted, Immunohistochemistry, Macrophage Activation, Male, Middle Aged, Multiple Sclerosis, Neurons, Pituitary-Adrenal System, RNA, Messenger, Vasopressins, In Situ Hybridization, Microglia

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