title: The protective effects of insulin-like growth factor-1 on neurochemical phenotypes of dorsal root ganglion neurons with BDE-209-induced neurotoxicity in vitro.
abstract: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment as contaminants, in which 2,2',3,3',4,4',5,5',6,6'-decabrominated diphenyl ether (BDE-209) is the most abundant PBDE found in human samples. BDE-209 has been shown to cause neurotoxicity of primary sensory neurons with few effective therapeutic options available. Here, cultured dorsal root ganglion (DRG) neurons were used to determine the therapeutic effects of insulin-like growth factor-1 (IGF-1) on BDE-209-induced neurotoxicity. The results showed that IGF-1 promoted neurite outgrowth and cell viability of DRG neurons with BDE-209-induced neurotoxicity. IGF-1 inhibited oxidative stress and apoptotic cell death caused by BDE-209 exposure. IGF-1 could reverse the decrease in growth-associated protein-43 (GAP-43) and calcitonin gene-related peptide (CGRP), but not neurofilament-200 (NF-200), expression resulting from BDE-209 exposure. The effects of IGF-1 could be blocked by the extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, either alone or in combination. IGF-1 may play an important role in neuroprotective effects on DRG neurons with BDE-209-induced neurotoxicity through inhibiting oxidative stress and apoptosis and regulating GAP-43 and CGRP expression of DRG neurons. Both ERK1/2 and PI3K/Akt signaling pathways were involved in the effects of IGF-1. Thus, IGF-1 might be one of the therapeutic agents on BDE-209-induced neurotoxicity.
authors.affiliation: 1 Department of Anatomy, Shandong University School of Medicine, Jinan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: 1 Department of Anatomy, Shandong University School of Medicine, Jinan, China.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Chen
authors.affiliation: 2 Department of Human Biology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: 3 Department of Orthopaedics, Shandong University Qilu Hospital, Jinan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: 1 Department of Anatomy, Shandong University School of Medicine, Jinan, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1 Department of Anatomy, Shandong University School of Medicine, Jinan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D005411:Flame Retardants / Q000633:toxicity*; D019922:GAP-43 Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D005411:Flame Retardants; D019922:GAP-43 Protein; D055768:Halogenated Diphenyl Ethers; D047428:Protein Kinase Inhibitors; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D015740:Calcitonin Gene-Related Peptide; C010902:decabromobiphenyl ether
keywords: Insulin-like growth factor-1; dorsal root ganglion; neuron; neurotoxicity; polybrominated diphenyl ether