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Antidepressant Imipramine Protects Bupivacaine‐Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Coactivation of TrkA and TrkB
Author(s) -
Guo Jianrong,
Wang Huan,
Tao Qiang,
Sun Shiyu,
Liu Li,
Zhang Jianping,
Yang Dawei
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26051
Subject(s) - tropomyosin receptor kinase a , tropomyosin receptor kinase b , trk receptor , low affinity nerve growth factor receptor , dorsal root ganglion , neurite , neurotoxicity , neurotrophin , chemistry , pharmacology , microbiology and biotechnology , receptor , medicine , biology , neuroscience , neurotrophic factors , in vitro , biochemistry , spinal cord , toxicity , organic chemistry
In our work, we used an in vitro culture model to investigate whether antidepressant imipramine (Ip) may protect bupivacaine (Bv)‐induced neurotoxicity in mouse dorsal root ganglion (DRG). Adult mouse DRG was treated with 5 mM Bv in vitro to induce neurotoxicity. DRG was then pre‐treated with Ip, prior to Bv, to examine its effects on protecting Bv‐induced DRG apoptosis and neurite degeneration. Ip‐induced dynamic changes in Trk receptors, including TrkA/B/C and phosphor (p‐)TrkA/B/C, were examined by qPCR and Western blot. TrkA and TrkB were inhibited by siRNAs to further investigate their functional role in Ip‐ and Bv‐treated DRG. Ip protected Bv‐induced apoptosis and neurite loss in DRG. Ip did not alter TrkA/B/C expressions, whereas significantly augmented protein productions of p‐TrkA and p‐TrkB, but not p‐TrkC. SiRNA‐mediated TrkA or TrkB downregulation inhibited Trk receptors, and reduced p‐TrkA and p‐TrkB in DRG. TrkA or TrkB downregulation alone had no effect on Ip‐induced protection in Bv‐injured DRG. However, co‐inhibition of TrkA and TrkB significantly ameliorated the protective effect of Ip on Bv‐induced apoptosis and neurite loss in DRG. Imipramine protected bupivacaine‐induced neurotoxicity in DRG, likely via the co‐activation of TrkA and TrkB signaling pathways. J. Cell. Biochem. 118: 3960–3967, 2017. © 2017 Wiley Periodicals, Inc.