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EPAC Negatively Regulates Myelination via Controlling Proliferation of Oligodendrocyte Precursor Cells

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A Correction to this article was published on 07 May 2020

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Abstract

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.

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  • 07 May 2020

    The original version of this article unfortunately contained a mistake.

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Acknowledgements

We thank Prof. You-Min Lu (Huazhong University of Science and Technology, Wuhan, China) for providing the original EPAC1 and EPAC2 knockout mice and the Core Facilities of Zhejiang University Institute of Neuroscience for technical assistance. This work was supported by the National Key Research and Development Program of Ministry of Technology and Science of China (2017YFA0104200), the National Natural Science Foundation of China (31560273, 81625006, 31571051, and 81571098), and the Natural Science Foundation of Zhejiang Province, China (Z15C090001).

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  1. Zhen-Zhen Gao and Ying-Cong Li contributed equally to this work.

Authors and Affiliations

  1. Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China

    Zhen-Zhen Gao & Jian Xiao

  2. Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Ying-Cong Li, Chong-Yu Shao, Ying Shen & Liang Zhou

  3. Key Laboratory of Brain Science, Guizhou Institution of Higher Education, Zunyi Medical University, Zunyi, 563000, China

    Liang Zhou

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  1. Zhen-Zhen Gao
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  4. Jian Xiao
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Correspondence to Ying Shen or Liang Zhou.

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Gao, ZZ., Li, YC., Shao, CY. et al. EPAC Negatively Regulates Myelination via Controlling Proliferation of Oligodendrocyte Precursor Cells. Neurosci. Bull. 36, 639–648 (2020). https://doi.org/10.1007/s12264-020-00495-6

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  • DOI: https://doi.org/10.1007/s12264-020-00495-6

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