Stemazole Promotes Oligodendrocyte Precursor Cell Survival In Vitro and Remyelination In Vivo

Int J Mol Sci. 2022 Sep 15;23(18):10756. doi: 10.3390/ijms231810756.

Abstract

Maintaining the normal function of oligodendrocyte precursor cells (OPCs) and protecting OPCs from damage is the basis of myelin regeneration in multiple sclerosis (MS). In this paper, we investigated the effect of stemazole, a novel small molecule, on the promotion of oligodendrocyte precursor cell survival and remyelination. The results show that stemazole enhanced the survival rate and the number of clone formation in a dose-dependent manner and decreased the percentage of cell apoptosis. In particular, the number of cell clones was increased up to 6-fold (p < 0.001) in the stemazole group compared with the control group. In vivo, we assessed the effect of stemazole on recovering the motor dysfunction and demyelination induced by cuprizone (CPZ). The results show that stemazole promoted the recovery of motor dysfunction and the repair of myelin sheaths. Compared with the CPZ group, the stemazole group showed a 30.46% increase in the myelin area (p < 0.001), a 37.08% increase in MBP expression (p < 0.01), and a 1.66-fold increase in Olig2 expression (p < 0.001). Histologically, stemazole had a better effect than the positive control drugs. In conclusion, stemazole promoted OPC survival in vitro and remyelination in vivo, suggesting that this compound may be used as a therapeutic agent against demyelinating disease.

Keywords: multiple sclerosis; oligodendrocyte precursor cells; remyelination; stemazole.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cuprizone / adverse effects
  • Demyelinating Diseases* / chemically induced
  • Demyelinating Diseases* / drug therapy
  • Demyelinating Diseases* / metabolism
  • Disease Models, Animal
  • Hydrazines
  • Mice
  • Mice, Inbred C57BL
  • Myelin Sheath / metabolism
  • Oligodendrocyte Precursor Cells* / metabolism
  • Oligodendroglia / metabolism
  • Oxadiazoles
  • Remyelination*

Substances

  • Hydrazines
  • Oxadiazoles
  • hydrazinecarbothioamide,N-(4-(4,5-dihydro-5-thioxo-1,3,4-oxadiazol-2-yl)phenyl)
  • Cuprizone

Grants and funding

This research was funded by the National Natural Science Foundation of China, grant numbers 81173139 and 30672491.