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Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination

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dc.contributor.author Wies Mancini, Victoria Sofía Berenice
dc.contributor.author Pasquini, Juana María
dc.contributor.author Correale, Jorge
dc.contributor.author Pasquini, Laura Andrea
dc.date.accessioned 2020-11-04T14:11:29Z
dc.date.available 2020-11-04T14:11:29Z
dc.date.issued 2018-11-19
dc.identifier.citation Wies Mancini, V.S.B., Pasquini, J.M., Correale, J.D., Pasquini, L.A. Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination. Glia 2019 Feb;67(2):291-308. doi: 10.1002/glia.23540. Epub 2018 Nov 19. en_US
dc.identifier.uri https://doi.org/10.1002/glia.23540
dc.identifier.uri https://repositorio.fleni.org.ar/handle/123456789/219
dc.description.abstract Multiple sclerosis (MS) is one of the most common causes of progressive disability affecting young people with very few therapeutic options available for its progressive forms. Its pathophysiology involves demyelination and neurodegeneration apparently driven by microglial activation, which is physiologically dependent on colony-stimulating factor-1 receptor (CSF-1R) signaling. In the present work, we used microglial modulation through oral administration of brain-penetrant CSF-1R inhibitor BLZ945 in acute and chronic cuprizone (CPZ)-induced demyelination to evaluate preventive and therapeutic effects on de/remyelination and neurodegeneration. Our results show that BLZ945 induced a significant reduction in the number of microglia. Preventive BLZ945 treatment attenuated demyelination in the acute CPZ model, mainly in cortex and external capsule. In contrast, BLZ945 treatment in the acute CPZ model failed to protect myelin or foster remyelination in myelin-rich areas, which may respond to a loss in microglial phagocytic capacity and the consequent impairment in oligodendroglial differentiation. Preventive and therapeutic BLZ945 treatment promoted remyelination and neuroprotection in the chronic model. These results could be potentially transferred to the treatment of progressive forms of MS. en_US
dc.language.iso eng en_US
dc.publisher Wiley en_US
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Microglia en_US
dc.subject Receptors, Colony-Stimulating Factor en_US
dc.subject Receptores del Factor Estimulante de Colonias en_US
dc.subject Demyelinating Diseases en_US
dc.subject Enfermedades Desmielinizantes en_US
dc.title Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination en_US
dc.type info:eu-repo/semantics/publishedVersion
dc.type info:eu-repo/semantics/article en_US
dc.description.fil Fil: Wies Mancini, Victoria Sofía Berenice. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina.
dc.description.fil Fil: Pasquini, Juana María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina.
dc.description.fil Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina
dc.description.fil Fil: Pasquini, Laura Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina.
dc.relation.ispartofVOLUME 67
dc.relation.ispartofNUMBER 2
dc.relation.ispartofPAGINATION 291-308
dc.relation.ispartofCOUNTRY Estados Unidos
dc.relation.ispartofCITY Nueva York
dc.relation.ispartofTITLE Glia
dc.relation.ispartofISSN 1098-1136
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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