Teriflunomide Promotes Oligodendroglial 8,9-Unsaturated Sterol Accumulation and CNS Remyelination
| Autor: | Brahim Nait Oumesmar, Catherine Lubetzki, Corinne Bachelin, Bruno Stankoff, Marie-Stéphane Aigrot, Elodie Martin, Bernard Zalc, Foudil Lamari |
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| Přispěvatelé: | Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, Hal Sorbonne Université |
| Rok vydání: | 2021 |
| Předmět: |
Zymosterol
MESH: Oligodendrocyte Precursor Cells Hydroxybutyrates MESH: Animals Newborn Mice Xenopus laevis Myelin chemistry.chemical_compound MESH: Cholesterol Central Nervous System Diseases Teriflunomide MESH: Animals MESH: Hydroxybutyrates Cells Cultured MESH: Toluidines MESH: Oligodendroglia MESH: Nitriles MESH: Crotonates Cell biology Oligodendroglia Cholesterol medicine.anatomical_structure Neurology Crotonates Larva [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] MESH: Immunosuppressive Agents Immunosuppressive Agents MESH: Cells Cultured MESH: Demyelinating Diseases Toluidines MESH: Mice Transgenic Mice Transgenic Article MESH: Mice Inbred C57BL MESH: Xenopus laevis In vivo Nitriles medicine Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Remyelination MESH: Mice Oligodendrocyte Precursor Cells MESH: Remyelination business.industry Multiple sclerosis Oligodendrocyte differentiation medicine.disease MESH: Central Nervous System Diseases Oligodendrocyte Mice Inbred C57BL Disease Models Animal Animals Newborn chemistry Neurology (clinical) MESH: Disease Models Animal business MESH: Larva Demyelinating Diseases |
| Zdroj: | Neurology Neuroimmunology & Neuroinflammation Neurology Neuroimmunology & Neuroinflammation, 2021, 8 (6), pp.e1091. ⟨10.1212/nxi.0000000000001091⟩ Neurology® Neuroimmunology & Neuroinflammation article-version (Version of Record) 3 |
| ISSN: | 2332-7812 |
| DOI: | 10.1212/nxi.0000000000001091 |
| Popis: | Background and ObjectivesTo test whether low concentrations of teriflunomide (TF) could promote remyelination, we investigate the effect of TF on oligodendrocyte in culture and on remyelination in vivo in 2 demyelinating models.MethodsThe effect of TF on oligodendrocyte precursor cell (OPC) proliferation and differentiation was assessed in vitro in glial cultures derived from neonatal mice and confirmed on fluorescence-activated cell sorting–sorted adult OPCs. The levels of the 8,9-unsaturated sterols lanosterol and zymosterol were quantified in TF- and sham-treated cultures. In vivo, TF was administered orally, and remyelination was assessed both in myelin basic protein–GFP-nitroreductase (Mbp:GFP-NTR) transgenic Xenopus laevis demyelinated by metronidazole and in adult mice demyelinated by lysolecithin.ResultsIn cultures, low concentrations of TF down to 10 nM decreased OPC proliferation and increased their differentiation, an effect that was also detected on adult OPCs. Oligodendrocyte differentiation induced by TF was abrogated by the oxidosqualene cyclase inhibitor Ro 48-8071 and was mediated by the accumulation of zymosterol. In the demyelinated tadpole, TF enhanced the regeneration of mature oligodendrocytes up to 2.5-fold. In the mouse demyelinated spinal cord, TF promoted the differentiation of newly generated oligodendrocytes by a factor of 1.7-fold and significantly increased remyelination.DiscussionTF enhances zymosterol accumulation in oligodendrocytes and CNS myelin repair, a beneficial off-target effect that should be investigated in patients with multiple sclerosis. |
| Databáze: | OpenAIRE |
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