Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord
Open accessAbstract
Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease. The presence of myelin lipid debris was seen only at the peak of EAE in demyelination loci being efficiently removed during the recovery period. Since CYP46A1 is responsible for removal of cholesterol excess, we performed a detailed profiling of CYP46A1 expression and revealed regional and temporal specificities in its distribution. Double immunofluorescence staining demonstrated CYP46A1 localization with neurons, infiltrated macrophages, microglia and astrocytes in the areas of demyelination, suggesting that these cells play a role in cholesterol turnover in EAE. We propose that alterations in the regulation of cholesterol metabolism at the onset and peak of EAE may add to the progression of disease, while during the recovery period may have beneficial effects contributing to the regeneration of myelin sheath and restoration of neuronal function.
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Metabolic derangements of cholesterol lead to microglial activation, chronic inflammation, and progression of neurodegenerative diseases.
“For example, metabolic derangements of cholesterol lead to microglial activation, chronic inflammation, and progression of NDs [65,66].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [66]
The Introduction (page not specified) says cholesterol may promote inflammatory-mediator production by macrophages, creating a cycle of inflammation. The Abstract (page not specified) suggests altered cholesterol metabolism may contribute to progression of experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Neither passage establishes that cholesterol derangements cause microglial activation and chronic inflammation or that this pathway drives neurodegenerative diseases generally. (LLM, conf=0.86)
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- Authors
- Lavrnja, I., Smiljanic, K., Savic, D., Mladenovic-Djordjevic, A., Tesovic, K., Kanazir, S., & Pekovic, S.
- Affiliations
- University of Belgrade (RS)
- Corresponding author
- Lavrnja, Irena
- Venue
- Scientific Reports
- Published
- 2017-06-02
- Volume
- 7
- Issue
- 1
- Pages
- 2702-2702
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5457442
- OpenAlex
- W2617811369
- Cited by
- 54
- References
- 58
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 7
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Digital Repository of Archived Publications (University of Belgrade, Institute for Biological Research Sinisa Stankovic) (submittedVersion, cc-by)
- Funders
- Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja (III 41014, OI173056, 41014)
- National Institutes of Health
- National Institute on Aging (R03AG046216)
- Fogarty International Center
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cholesterol metabolism, experimental autoimmune encephalomyelitis, multiple sclerosis, spinal cord, CYP46A1, cholesterol 24-hydroxylase, HMGCR, apolipoprotein E, demyelination, myelin debris, microglia, macrophages, astrocytes, remyelination
- MeSH terms
- Cholesterol 24-Hydroxylase, Animals, Astrocytes, Cholesterol, Demyelinating Diseases, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Macrophages, Multiple Sclerosis, Neurons, Phenotype, Severity of Illness Index, Spinal Cord, Biomarkers, Gene Expression, Microglia, Disease Progression, Lipid Metabolism, Rats, Transcriptome
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