title: Antidepressant Imipramine Protects Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Coactivation of TrkA and TrkB.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Gongli Hospital, Second Military Medical University, Shanghai, 200135, China.
authors.forename: Jianrong
authors.identifier: 0000-0003-3780-5622
authors.initials: J
authors.lastname: Guo
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tao
authors.forename: Shiyu
authors.initials: S
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Gongli Hospital, Second Military Medical University, Shanghai, 200135, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Yang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002045:Bupivacaine / Q000009:adverse effects* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D007099:Imipramine / Q000494:pharmacology*; D051379:Mice; D016501:Neurites / Q000201:enzymology* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D020917:Receptor, trkA / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D020917:Receptor, trkA; D020813:Receptor, trkB; D007099:Imipramine; D002045:Bupivacaine
keywords: BUPIVACAINE; DORSAL ROOT GANGLION; NEUROTOXICITY; TrkA; TrkB; TrkC