Saturday, 10 June 2017

Cholestero-related genes in EAE

Lavrnja I, Smiljanic K, Savic D, Mladenovic-Djordjevic A, Tesovic K, Kanazir S, Pekovic S. Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord.
Sci Rep. 2017;7(1):2702

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.


This is another study implicating cholesterol in the control of EAE, as we have previously reported
Sevastou I, Pryce G, Baker D, Selwood DL. Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing.PLoS One. 2016 Jun 29;11(6):e0157754. However there was no change in CYP46A1 in the progressive disease.  This study however looked during active disease.

1 comment:

  1. And I've read some studies on EBV deregulating Cholesterol and need it to survive.

    https://www.ncbi.nlm.nih.gov/pubmed/17150237

    Now really in my family people or have cardiovascular problems or have problem with cholesterol, my father for example has atherosclerosis.

    Now reading about cholesterol, oral contraceptives can interfere with cholesterol because progesterone raises LDL (bad cholesterol) levels. Could that say anything about women using oral contraceptives before CIS?

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