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

Autor: Laura A. Pasquini, Juana M. Pasquini, Jorge Correale, Victoria Sofía Berenice Wies Mancini
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Time Factors
External capsule
Nitric Oxide Synthase Type II
Nerve Tissue Proteins
Pharmacology
Biology
Neuroprotection
MICROGLIA
Ciencias Biológicas
Colony stimulating factor 1 receptor
Cuprizone
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
Myelin
0302 clinical medicine
Microscopy
Electron
Transmission
Receptors
Colony-Stimulating Factor
medicine
Animals
Benzothiazoles
Remyelination
Picolinic Acids
MULTIPLE SCLEROSIS
Amyloid beta-Peptides
Microglia
Multiple sclerosis
Neurodegeneration
Brain
Myelin Basic Protein
Bioquímica y Biología Molecular
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Bromodeoxyuridine
Neurology
CUPRIZONE
Cytokines
DEMYELINATION-REMYELINATION
BLZ945
CIENCIAS NATURALES Y EXACTAS
030217 neurology & neurosurgery
CSF-1R
Demyelinating Diseases
Zdroj: Glia. 67:291-308
ISSN: 0894-1491
DOI: 10.1002/glia.23540
Popis: 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. Fil: Wies Mancini, Victoria Sofia Berenice. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Correale, Jorge Daniel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Pasquini, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Databáze: OpenAIRE
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