title: Amitriptyline Activates TrkA to Aid Neuronal Growth and Attenuate Anesthesia-Induced Neurodegeneration in Rat Dorsal Root Ganglion Neurons.
abstract: Tricyclic antidepressant amitriptyline (AM) has been shown to exert neurotrophic activity on neurons. We thus explored whether AM may aid the neuronal development and protect anesthesia-induced neuro-injury in young spinal cord dorsal root ganglion (DRG) neurons.The DRG explants were prepared from 1-day-old rats. The effect of AM on aiding DRG neural development was examined by immunohistochemistry at dose-dependent manner. AM-induced changes in gene and protein expressions, and also phosphorylation states of tyrosine kinases receptor A (TrkA) and B (TrkB) in DRG, were examined by quantitative real-time polymerase chain reaction and western blot. The effect of AM on attenuating lidocaine-induced DRG neurodegeneration was examined by immunohistochemistry, and small interfering RNA (siRNA)-mediated TrkA/B down-regulation.Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10 M. AM activated TrkA in DRG through phosphorylation, whereas it had little effect on TrkB-signaling pathway. AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones. Moreover, the neuroprotection of AM on lidocaine-injured neurodegeneration was blocked by siRNA-mediated TrkA down-regulation, but not by TrkB down-regulation.Amitriptyline facilitated neuronal development and had protective effect on lidocaine-induced neurodegeneration, very likely through the activation of TrkA-signaling pathway in DRG.
authors.affiliation: From the Department of Anesthesiology (XZ, FC, TZ, FH, JC, WT), Provincial Clinical Medical College, Fujian Medical University, Fujian Provincial Hospital; and Fujian Provincial Emergency Center (FC), Provincial Clinical Medical College, Fujian Medical University, Fuzhou, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zheng
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.forename: Fengyi
authors.initials: F
authors.lastname: Huang
authors.forename: Jianghu
authors.initials: J
authors.lastname: Chen
authors.forename: Wenshao
authors.initials: W
authors.lastname: Tu
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000254:growth & development; D008012:Lidocaine / Q000009:adverse effects*; D009410:Nerve Degeneration / Q000139:chemically induced*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020917:Receptor, trkA / Q000187:drug effects* / Q000502:physiology; D020813:Receptor, trkB / Q000187:drug effects / Q000502:physiology
chemical_list: D000779:Anesthetics, Local; D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D008012:Lidocaine; D020917:Receptor, trkA; D020813:Receptor, trkB