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

Main Points• CSF‐1R inhibitor BLZ945 reduces the number of microglial cells• BLZ945 reduces myelin damage in acute CPZ‐induced demyelination mainly in myelin‐poor areas• BLZ945 promotes remyelination and neuroprotection in chronic CPZ‐induced demyelination AbstractMultiple 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/rem yelination 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 t o 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 i...

Source: Glia - November 19, 2018 Category: Neurology Authors: Victoria Sof ía Berenice Wies Mancini, Juana María Pasquini, Jorge Daniel Correale, Laura Andrea Pasquini Tags: RESEARCH ARTICLE Source Type: research