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Downregulation of miR-210 protected bupivacaine-induced neurotoxicity in dorsal root ganglion

Experimental Brain Research volume 234, pages 1057–1065 (2016)Cite this article

Abstract

Local anesthetic may cause neurotoxicity in developing neurons. In this study, we examined the molecular mechanisms of microRNA-210 (miR-210) in regulating bupivacaine-induced dorsal root ganglia (DRG) neurotoxicity in vitro. Young mouse (P30) DRG explants were cultured in vitro and treated with 5 mM bupivacaine to induce neurotoxicity. QRT-PCR was used to evaluate the expression profiles of miRNAs within 24 h after bupivacaine treatment. MiR-210 was downregulated in DRG, and its effects on bupivacaine-induced neurotoxicity were evaluated by apoptosis and neurite growth assays, respectively. Putative downstream target of miR-210 in DRG, BDNF, was evaluated by dual-luciferase assay, qRT-PCR, and western blot, respectively. BDNF was then knocked down by siRNA to assess its associated effects in regulating DRG neurotoxicity. Within the initial 24 h after bupivacaine treatment, various patterns of miRNA expression were observed, whereas miR-210 was constantly upregulated. Application of miR-210 inhibitor efficiently downregulated endogenous miR-210, protected apoptosis and neurite retraction in bupivacaine damaged DRG neurons. Using dual-luciferase assay, qRT-PCR, and western blot, BDNF was confirmed to the downstream target of miR-210 in DRG. SiRNA-mediated BDNF downregulation reversed the effect of miR-210 downregulation in DRG neurotoxicity. MiR-210, through the regulation of BDNF, plays important role in anesthetics-induced DRG neurotoxicity.

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Authors and Affiliations

  1. College of Clinical Medicine, Jilin University, Changchun, 130021, China

    Yiheng Wang & Haishan Zhang

  2. Basic Medical College, Beihua University, Jilin, 132000, China

    Hongxia Ni

  3. Department of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, China

    Wenrui Zhang

  4. Endoscopy Center, The First Hospital of Jilin University, Changchun, 130021, China

    Xiu Wang

  5. Department of Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai St., Changchun, 130033, China

    Haishan Zhang

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  1. Yiheng Wang
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  2. Hongxia Ni
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  3. Wenrui Zhang
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  4. Xiu Wang
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  5. Haishan Zhang
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Correspondence to Haishan Zhang.

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Wang, Y., Ni, H., Zhang, W. et al. Downregulation of miR-210 protected bupivacaine-induced neurotoxicity in dorsal root ganglion. Exp Brain Res 234, 1057–1065 (2016). https://doi.org/10.1007/s00221-015-4513-4

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  • DOI: https://doi.org/10.1007/s00221-015-4513-4

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