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 (EPAC^dKO) 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.

中文翻译：

---

EPAC通过控制少突胶质前体细胞的增殖来负调节髓鞘形成。

越来越多的证据表明，依赖环磷酸腺苷（cAMP）的细胞内信号驱动髓鞘形成过程。然而，cAMP对中枢神经系统髓鞘形成作用的信号转导仍未确定。在目前的工作中，我们试图确定EPAC（cAMP激活的交换蛋白），cAMP的下游效应物，在使用EPAC1和EPAC2双敲^除法（EPAC ^dKO）形成髓鞘的过程中的^作用。） 老鼠。结果显示EPAC1和EPAC2对髓磷脂的发育具有年龄依赖性，因为它们的缺乏会引起出生后早期成年小鼠而不是晚期成年小鼠产生更多的髓鞘。EPAC的敲除促进少突胶质细胞前体细胞的增殖，并且对髓鞘相关转录因子具有多种作用，进而增加了髓鞘相关蛋白的表达。这些结果表明，EPAC蛋白是髓鞘形成的负调节剂，并且可能是治疗髓鞘相关疾病的有希望的靶标。