Effect of Notch1 gene on remyelination in multiple sclerosis in mouse models of acute demyelination.

Abstract

This study aims to explore the effects of Notch1 gene on remyelination in multiple sclerosis (MS). A mouse model of acute demyelination was successfully established and the model mice were grouped as cuprizone (CPZ) group, CPZ + small interfering RNA (siRNA)-Notch1 (siNotch1) group, and CPZ + siRNA negative control (NC) group. Meanwhile, another 3 groups (control, control + siNotch1, and control + siRNA NC) were established in normal mice. The changes of weight and maintenance time in rotating drum of mice were observed. Western blot analysis for the protein expressions related to Notch signaling pathway and oligodendrocyte (OL) differentiation in the corpus callosum of the mice. After model establishment, the weight of CPZ-induced demyelinated mice was decreased. During the repair period, the balance ability and movement of the mice was recovered, especially for those injected with siNotch1 plasmid. After model establishment, the number of myelinated axons was decreased. In comparison with the CPZ and CPZ siRNA NC groups, the CPZ + siNotch1 group had a decrease in the number of premature OLs, but increase in mature OLs, and a decrease in oligodendrocyte precursor cells and astrocytes. The expressions of proteins related to Notch signaling pathway, such as HES, Jagged-1 were decreased in the CPZ + siNotch1 group in contrast to the CPZ and CPZ + siRNA groups, but the OL-related transcription factor Sox10 was increased in the CPZ + siNotch1 group than in the CPZ + siRNA NC and CPZ groups, and Id2 was decreased. Our study provided evidence that the inhibition of Notch1 gene could accelerate remyelination in MS.