Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis
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 dys...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02409-x |
| _version_ | 1818284213560934400 |
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| author | Solenne Vigne Donovan Duc Benjamin Peter Jessica Rebeaud Yannick Yersin Florian Ruiz Valentine Bressoud Tinh-Hai Collet Caroline Pot |
| author_facet | Solenne Vigne Donovan Duc Benjamin Peter Jessica Rebeaud Yannick Yersin Florian Ruiz Valentine Bressoud Tinh-Hai Collet Caroline Pot |
| author_sort | Solenne Vigne |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T00:49:14Z |
| format | Article |
| id | doaj.art-bcf2ff87b9074735a9b5e0413603412d |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T00:49:14Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-bcf2ff87b9074735a9b5e0413603412d2022-12-22T00:04:57ZengBMCJournal of Neuroinflammation1742-20942022-02-0119111210.1186/s12974-022-02409-xLowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitisSolenne Vigne0Donovan Duc1Benjamin Peter2Jessica Rebeaud3Yannick Yersin4Florian Ruiz5Valentine Bressoud6Tinh-Hai Collet7Caroline Pot8Laboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneLaboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneLaboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneLaboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneLaboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneLaboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneLaboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneService of Endocrinology, Diabetes, Nutrition and Therapeutic Education, Department of Medicine, Geneva University Hospitals (HUG)Laboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneAbstract 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.https://doi.org/10.1186/s12974-022-02409-xAutoimmunityMultiple sclerosisEAENeuroinflammationCholesterolHypercholesterolemia |
| spellingShingle | Solenne Vigne Donovan Duc Benjamin Peter Jessica Rebeaud Yannick Yersin Florian Ruiz Valentine Bressoud Tinh-Hai Collet Caroline Pot Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis Journal of Neuroinflammation Autoimmunity Multiple sclerosis EAE Neuroinflammation Cholesterol Hypercholesterolemia |
| title | Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis |
| title_full | Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis |
| title_fullStr | Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis |
| title_full_unstemmed | Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis |
| title_short | Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis |
| title_sort | lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis |
| topic | Autoimmunity Multiple sclerosis EAE Neuroinflammation Cholesterol Hypercholesterolemia |
| url | https://doi.org/10.1186/s12974-022-02409-x |
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