EPAC Negatively Regulates Myelination via Controlling Proliferation of Oligodendrocyte Precursor Cells

Increasing evidence suggests that a cyclic adenosine monophosphate(cAMP)-dependent intracellular signal drives the process of myelination.Yet,the signal transduction underlying the action of cAMP on central nervous system myelination remains undefined.In the present work,we sought to determine the role of EPAC(exchange protein activated by cAMP),a downstream effector of cAMP,in the development of the myelin sheath using EPAC1 and EPAC2 double-knockout(EPACdKO)mice.The results showed an age-dependent regulatory effect of EPAC1 and EPAC2 on myelin development,as their deficiency caused more myelin sheaths in postnatal early but not late adult mice.Knockout of EPAC promoted the proliferation of oligodendrocyte precursor cells and had diverse effects on myelin-related transcription factors,which in turn increased the expression of myelin-related proteins.These results indicate that EPAC proteins are negative regulators of myelination and may be promising targets for the treatment of myelin-related diseases.