Potential associations between immune signaling genes, deactivated microglia, and oligodendrocytes and cortical gray matter loss in patients with long-term remitted cushing’s disease
Open accessAbstract
INTRODUCTION: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients compared to healthy controls, specifically in the anterior cingulate cortex (ACC). However, potential mechanisms through which these persistent alterations may have occurred are currently unknown. METHODS: Structural 3T MRI's from 25 remitted CD patients were linked with gene expression data from neurotypical donors, derived from the Allen Human Brain Atlas. Differences in gene expression between the ACC and an unaffected control cortical region were examined, followed by a Gene Ontology (GO) enrichment analysis. A cell type enrichment analysis was conducted on the differentially expressed genes, and a disease association enrichment analysis was conducted to determine possible associations between differentially expressed genes and specific diseases. Subsequently, cortisol sensitivity of these genes in existing datasets was examined. RESULTS: The gene expression analysis identified 300 differentially expressed genes in the ACC compared to the cortical control region. GO analyses found underexpressed genes to represent immune function. The cell type specificity analysis indicated that underexpressed genes were enriched for deactivated microglia and oligodendrocytes. Neither significant associations with diseases, nor evidence of cortisol sensitivity with the differentially expressed genes were found. DISCUSSION: Underexpressed genes in the ACC, the area vulnerable to permanent changes in remitted CD patients, were often associated with immune functioning. The specific lack of deactivated microglia and oligodendrocytes implicates protective effects of these cell types against the long-term effects of cortisol overexposure.
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Glucocorticoids may modulate the brain indirectly through their effects on the immune system, metabolism, sleep, other hormones, and the gut microbiota.
“Furthermore, glucocorticoids may modulate the brain indirectly through their effects on the immune system, metabolism, sleep, other hormones, and the GM (432, 433).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [432]
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References 80 · Cited by 9
Research works printed but not linked: 1
- Alonso, G., 2000. Prolonged corticosterone treatment of adult rats inhibits the proliferation of oligodendrocyte progenitors present throughout white and gray matter regions of the brain. Glia 31 (3), 219-231.
- Authors
- Bauduin, S. E. E. C., den Rooijen, I. L. B., Meijer, M., van der Werff, S. J. A., Keo, A., Dzyubachyk, O., Pereira, A. M., Giltay, E. J., van der Wee, N. J. A., Meijer, O. C., & Mahfouz, A.
- Affiliations
- Leiden University (NL)
- Radboud University Nijmegen (NL)
- Leiden University Medical Center (NL)
- Corresponding author
- Mahfouz, A.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 132
- Pages
- 105334
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W3175716393
- Cited by
- 9
- References
- 80
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 4 · 2022: 1
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc-nd)
- Radboud Repository (Radboud University) (submittedVersion)
- Research Repository (Delft University of Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Cushing's disease, remission, hypercortisolism, anterior cingulate cortex, oligodendrocytes, gene expression, neuroendocrine diseases, brain structural changes
- MeSH terms
- Cerebral Cortex, Humans, Hydrocortisone, Immunity, Oligodendroglia, Microglia, Pituitary ACTH Hypersecretion, Gray Matter
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