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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

Open Access 01-12-2022 | Multiple Sclerosis | Research

Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis

Authors: Solenne Vigne, Donovan Duc, Benjamin Peter, Jessica Rebeaud, Yannick Yersin, Florian Ruiz, Valentine Bressoud, Tinh-Hai Collet, Caroline Pot

Published in: Journal of Neuroinflammation | Issue 1/2022

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Abstract

Background

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) commonly affecting young adults. There is increasing evidence that environmental factors are important in the development and course of MS. The metabolic syndrome (MetS) which comprises dyslipidemia has been associated with a worse outcome in MS disease. Furthermore, the lipid-lowering drug class of statins has been proposed to improve MS disease course. However, cholesterol is also rate-limiting for myelin biogenesis and promotes remyelination in MS animal models. Thus, the impact of circulating blood cholesterol levels during the disease remains debated and controversial.

Methods

We assessed the role of circulating cholesterol on the murine model of MS, the experimental autoimmune encephalomyelitis (EAE) disease using two different approaches: (1) the mouse model of familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, and (2) the use of the monoclonal anti-PCSK9 neutralizing antibody alirocumab, which reduces LDLr degradation and consequently lowers blood levels of cholesterol.

Results

Elevated blood cholesterol levels induced by LDLr deficiency did not worsen clinical symptoms of mice during EAE. In addition, we observed that the anti-PCSK9 antibody alirocumab did not influence EAE disease course, nor modulate the immune response in EAE.

Conclusions

These findings suggest that blood cholesterol level has no direct role in neuro-inflammatory diseases and that the previously shown protective effects of statins in MS are not related to circulating cholesterol.
Appendix
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Metadata
Title
Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis
Authors
Solenne Vigne
Donovan Duc
Benjamin Peter
Jessica Rebeaud
Yannick Yersin
Florian Ruiz
Valentine Bressoud
Tinh-Hai Collet
Caroline Pot
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-022-02409-x

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