Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord
2017
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Authors:
Lavrnja, IrenaSmiljanić, Kosara
Savić, Danijela
Mladenović, Aleksandra
Milošević, Katarina
Kanazir, Selma
Peković, Sanja
Document Type:
Article (Published version)
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Show full item recordAbstract:
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.
Keywords:
Astrocyte; Multiple sclerosisFunding / projects:
- Brain plasticity in aging: effect of dietary restriction and anesthesia (RS-MESTD-Basic Research (BR or ON)-173056)
- Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41014)
- Fogarty International Research Award, NIH (R03AG046216)
In:
- Scientific Reports (2017), 7(1): 2702
DOI: 10.1038/s41598-017-02638-8
ISSN: 2045-2322
PubMed: 28578430
WoS: 000402515800020
Scopus: 2-s2.0-85020164924
URI
http://www.nature.com/articles/s41598-017-02638-8https://radar.ibiss.bg.ac.rs/handle/123456789/2760