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Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway

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Abstract

Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca2+ imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL induced increases in the [Ca2+] i level, Bdnf mRNA transcription, cAMP-response element-binding protein (CREB) phosphorylation, and extracellular signal-regulated kinase (ERK) phosphorylation, mediated by Ca2+ release via inositol triphosphate receptor (IP3R)-sensitive calcium (Ca2+) stores. Blockade of Ca2+ increase suppressed Bdnf mRNA transcription, CREB phosphorylation, and ERK phosphorylation. Downregulation of phosphorylated (p)-CREB reduced Bdnf mRNA transcription triggered by LLL. Furthermore, blockade of ERK using PD98059 inhibitor reduced p-CREB and Bdnf mRNA transcription induced by LLL. Taken together, these findings establish the Ca2+-ERK-CREB cascade as a potential signaling pathway involved in LLL-induced Bdnf mRNA transcription. To our knowledge, this is the first report of the mechanisms of Ca2+-dependent Bdnf mRNA transcription triggered by LLL. These findings may help further explore the complex molecular signaling networks in LLL-triggered nerve regeneration in vivo and may also provide experimental evidence for the development of LLL for clinical applications.

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Acknowledgments

The authors acknowledge Wei Hu, Li Liang, and Ruichen Wang for technical support.

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    Authors and Affiliations

    1. Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi’an, 710038, China

      Xiaodong Yan, Siguo Sun, Jian Zhao, Xin Dong, Jixian Qian & Honghui Sun

    2. Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi’an, 710032, China

      Juanfang Liu

    3. Department of Orthopaedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710054, China

      Zhengping Zhang

    4. Cadet Brigade, Fourth Military Medical University, Xi’an, 710032, China

      Wenhao Li

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    1. Xiaodong Yan
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    Correspondence to Jixian Qian or Honghui Sun.

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    All the experimental procedures for animals were conducted under a protocol reviewed and approved by the Committee on the Ethics of Animal Experiments of the Tangdu Hospital, Fourth Military Medical University.

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    This study was supported in part by the Natural Science Basic Research Project of Shaanxi Province (No. 2014JQ4115) and National Natural Science Foundation of China (No. 81401001; No. 81272073; No. 81300926).

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    The authors declare that they have no conflict of interest.

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    Xiaodong Yan and Juanfang Liu contributed equally to this work.

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    Yan, X., Liu, J., Zhang, Z. et al. Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway. Lasers Med Sci 32, 169–180 (2017). https://doi.org/10.1007/s10103-016-2099-0

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