Olesoxime accelerates myelination and promotes repair in models of demyelination

Autor: Karine Magalon, Rebecca M. Pruss, Myriam Cayre, Clarisse Bourbon, Joseph Khaldi, Pascale Durbec, Angèle Viola, Isabelle Robles, Céline Zimmer, Thierry Bordet, Gwenaëlle Tardif
Přispěvatelé: Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Trophos S.A., Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2012
Předmět:
MESH: Myelin Sheath
MESH: Rats
Sprague-Dawley
MESH: Magnetic Resonance Imaging
Rats
Sprague-Dawley
chemistry.chemical_compound
Myelin
Mice
0302 clinical medicine
MESH: Animals
MESH: Cuprizone
Myelin Sheath
0303 health sciences
MESH: Oligodendroglia
Magnetic Resonance Imaging
3. Good health
Oligodendroglia
medicine.anatomical_structure
Neurology
Olesoxime
MESH: Demyelinating Diseases
Monoamine Oxidase Inhibitors
Multiple Sclerosis
MESH: Rats
Central nervous system
MESH: Monoamine Oxidase Inhibitors
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Neuroprotection
03 medical and health sciences
Cuprizone
MESH: Cholestenones
MESH: Mice
Inbred C57BL
medicine
Animals
Remyelination
MESH: Mice
Cholestenones
030304 developmental biology
Regeneration (biology)
Multiple sclerosis
MESH: Multiple Sclerosis
medicine.disease
Oligodendrocyte
Rats
Mice
Inbred C57BL
Disease Models
Animal
chemistry
nervous system
Neurology (clinical)
MESH: Disease Models
Animal
Neuroscience
030217 neurology & neurosurgery
Demyelinating Diseases
Zdroj: Annals of Neurology
Annals of Neurology, Wiley, 2012, 71 (2), pp.213-26. ⟨10.1002/ana.22593⟩
Annals of Neurology, 2012, 71 (2), pp.213-26. ⟨10.1002/ana.22593⟩
ISSN: 1531-8249
0364-5134
DOI: 10.1002/ana.22593⟩
Popis: Objective: Multiple sclerosis is a neurodegenerative disease characterized by episodes of immune attack of oligodendrocytes leading to demyelination and progressive functional deficit. One therapeutic strategy to address disease progression could consist in stimulating the spontaneous regenerative process observed in some patients. Myelin regeneration requires endogenous oligodendrocyte progenitor migration and activation of the myelination program at the lesion site. In this study, we have tested the ability of olesoxime, a neuroprotective and neuroregenerative agent, to promote remyelination in the rodent central nervous system in vivo. Methods: The effect of olesoxime on oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis was tested directly in organotypic slice cultures and OPC–neuron cocultures. Using naive animals and different mouse models of demyelination, we morphologically and functionally assessed the effect of the compound on myelination in vivo. Results: Olesoxime accelerated oligodendrocyte maturation and enhanced myelination in vitro and in vivo in naive animals during development and also in the adult brain without affecting oligodendrocyte survival or proliferation. In mouse models of demyelination and remyelination, olesoxime favored the repair process, promoting myelin formation with consequent functional improvement. Interpretation: Our observations support the strategy of promoting oligodendrocyte maturation and myelin synthesis to enhance myelin repair and functional recovery. We also provide proof of concept that olesoxime could be useful for the treatment of demyelinating diseases. ANN NEUROL 2012;71:213–226
Databáze: OpenAIRE
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