title: Neuroprotective effect of insulin-like growth factor-1: effects on tyrosine kinase receptor (Trk) expression in dorsal root ganglion neurons with glutamate-induced excitotoxicity in vitro.
abstract: Insulin-like growth factor-1 (IGF-1) may play an important role in regulating the expression of distinct tyrosine kinase receptor (Trk) in primary sensory dorsal root ganglion (DRG) neurons. Glutamate (Glu) is the main excitatory neurotransmitter and induces neuronal excitotoxicity for primary sensory neurons. It is not known whether IGF-1 influences expression of TrkA, TrkB, and TrkC in DRG neurons with excitotoxicity induced by Glu. In the present study, primary cultured DRG neurons with Glu-induced excitotoxicity were used to determine the effects of IGF-1 on TrkA, TrkB, and TrkC expression. The results showed that IGF-1 increased the expression of TrkA and TrkB and their mRNAs, but not TrkC and its mRNA, in primary cultured DRG neurons with excitotoxicity induced by Glu. Interestingly, neither the extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 nor the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 blocked the effect of IGF-1, but both inhibitors together were effective. IGF-1 may play an important role in regulating different Trk receptor expression in DRG neurons through ERK1/2 and PI3K/Akt signaling pathways. The contribution of distinct Trk receptors might be one of the mechanisms that IGF-1 rescues dying neurons from Glu excitotoxic injury. These data imply that IGF-1 signaling might be a potential target on modifying distinct Trk receptor-mediated biological effects of primary sensory neurons with excitotoxicity.
authors.affiliation: Department of Anatomy, Shandong University School of Medicine, Jinan 250012, China. lihao462929@163.com
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Haixia
authors.initials: H
authors.lastname: Dong
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
authors.forename: Huaxiang
authors.initials: H
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000633:toxicity; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC
keywords: Dorsal root ganglion; Glutamate; Insulin-like growth factor-1; Neurotoxicity; Tyrosine kinase receptor