Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis

• DOI: 10.1186/s12974-022-02409-x
• Publication Date: 2022-02-07T19:03:57Z
• Authors: Solenne Vigne; Donovan Duc; Benjamin Peter; Jessica Rebeaud; Yannick Yersin; Florian Ruiz; Valentine Bressoud; Tinh-Hai Collet; Caroline Pot
• Keywords: Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; EAE; Research; Hypercholesterolemia; LDL receptor; Autoimmunity; PCSK9; Multiple sclerosis; Mice; Cholesterol; Animals; Encephalomyelitis, Autoimmune, Experimental/drug therapy; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use; Hypercholesterolemia/metabolism; Mice; Multiple Sclerosis; Neuroinflammatory Diseases; Alirocumab; Autoimmunity; Cholesterol; EAE; Hypercholesterolemia; LDL receptor; Multiple sclerosis; Neuroinflammation; PCSK9; Neuroinflammation; info:eu-repo/classification/ddc/616; Neuroinflammatory Diseases; Animals; Neurology. Diseases of the nervous system; Hydroxymethylglutaryl-CoA Reductase Inhibitors; RC346-429; Alirocumab

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) commonly affecting young adults. There increasing evidence that environmental factors are important in development and course MS. The metabolic syndrome (MetS) which comprises dyslipidemia has been associated with worse outcome MS disease. Furthermore, lipid-lowering drug class statins proposed to improve course. However, cholesterol also rate-limiting for myelin biogenesis promotes remyelination animal models. Thus, impact circulating blood levels during remains debated controversial.We assessed role on murine model MS, experimental autoimmune encephalomyelitis (EAE) using two different approaches: (1) mouse familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, (2) use monoclonal anti-PCSK9 neutralizing antibody alirocumab, reduces LDLr degradation consequently lowers cholesterol.Elevated deficiency did not worsen clinical symptoms mice EAE. In addition, we observed alirocumab influence EAE course, nor modulate immune response EAE.These findings suggest level no direct neuro-inflammatory diseases previously shown protective effects related cholesterol.