Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord.

Authors: Lavrnja, Irena  Smiljanic, Kosara  Savic, Danijela  Mladenovic-Djordjevic, Aleksandra  Tesovic, Katarina  Kanazir, Selma  Pekovic, Sanja 
Citation: Lavrnja I, etal., Sci Rep. 2017 Jun 2;7(1):2702. doi: 10.1038/s41598-017-02638-8.
Pubmed: (View Article at PubMed) PMID:28578430
DOI: Full-text: DOI:10.1038/s41598-017-02638-8

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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CRRD Object Information
CRRD ID: 13703134
Created: 2018-08-03
Species: All species
Last Modified: 2018-08-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.