Effect of CSF1R Inhibitor on Glial Cells Population and Remyelination in The Cuprizone Model

Abstract Multiple sclerosis is a kind of autoimmune and demyelinating disease and its pathological symptoms include inflammation, myelin loss, astrocytosis, and microgliosis. The colony stimulating factor 1 receptor (CSF1R), as an essential factor for the microglial function, and PLX3397 is its specific inhibitor. In this study, we assessed the effect of different doses of PLX3397 for microglial ablation on glial cells population and remyelination process. Sixty male C57BL/6 mice (8 weeks old) were divided into 6 groups. The animals were fed with 0.2% cuprizone diet for 12 weeks for chronic demyelination model induction. For microglial ablation, PLX3397 (290 mg/kg) was added to the animal food for 3, 7, 14 and 21 days. Glial cells number was measured using immunohistochemistry. We evaluated the rate of remyelination using electron microscopy and Luxol Fast Blue staining. The expression levels of all genes were assessed by qRT-PCR method. Data were analysed using Graph pad prism and SPSS software.Data showed that the administration of different doses of PLX3397 significantly (p˂0.001) reduced microglial cells. PLX3397 administration significantly (p˂0.001) increased oligodendrocytes population with along rise of the remyelination compared to the cuprizone mice, which was confirmed by the results of LFB and TEM. Gene results showed that PLX3397 treatment reduced CSF1R expression. According to results, the administration of PLX3397 for 21 days enhanced remyelination by increasing oligodendrocytes in the chronic demyelination model. These positive effects could be related to the reduction of microglia.