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AMPK Negatively Regulates Peripheral Myelination via Activation of c-Jun

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Abstract

The process of Schwann cells (SCs) forming a sheath around axons is termed as myelination, which plays a pivotal role for proper physiological function in the peripheral nervous system (PNS). The molecular mechanisms regulating SC myelination in the PNS remain to be elucidated. Here, we show that AMP-activated protein kinase (AMPK) in sciatic nerves was gradually decreased during the PNS myelination process. Pharmacological interventions showed that activation of AMPK by AICAR attenuated myelin gene expression in SCs, whereas inhibition of AMPK by Compound C (ComC) or AMPKα1 knockdown stimulated myelin gene expression. Following experiments revealed that c-Jun, a negative modulator of PNS myelination, was activated by AMPK in SCs. The application of ComC in newborn rats markedly downregulated c-Jun expression in sciatic nerves. The lipid and protein synthesis in sciatic nerves was greatly potentiated by ComC. As a consequence, myelin gene expression in sciatic nerves, as well as myelin sheath thickness, were promoted in the ComC-treated rats. All together, our data identify that AMPK is an important negative regulator of Schwann cell myelination in the PNS, and this regulation role may rely on c-Jun activation.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (31271260, 81471037), the Basic Research Program of Jiangsu Education Department (14KJA180006), the Ph.D. Program Foundation of Ministry of Education of China (20110091120029), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

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    Authors and Affiliations

    1. Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People’s Republic of China

      Xiaoyu Liu, Su Peng, Yahong Zhao, Tingting Zhao, Meihong Wang, Yumin Yang & Cheng Sun

    2. Department of Geratology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Lan Luo

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    1. Xiaoyu Liu
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    Correspondence to Yumin Yang or Cheng Sun.

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    All of the animal protocols were approved by the Animal Care and Use Committee of Nantong University and the Jiangsu Province Animal Care Ethics Committee. The procedures for sciatic nerve injury model in rats were carried out in accordance with the approved guidelines.

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    The authors declare that they have no competing interests.

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    Xiaoyu Liu and Su Peng contributed equally to this work.

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    Liu, X., Peng, S., Zhao, Y. et al. AMPK Negatively Regulates Peripheral Myelination via Activation of c-Jun. Mol Neurobiol 54, 3554–3564 (2017). https://doi.org/10.1007/s12035-016-9913-3

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