title: The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro.
abstract: Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.
authors.affiliation: Department of Neurology, Shandong University Affiliated Shandong Provincial Hospital, Jinan 250021.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Computer Tomography and Magnetic Resonance Imaging, Weifang Medical College Affiliated Yidu Central Hospital, Qingzhou 262500.
authors.forename: Haixia
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Histology and Embryology, Binzhou Medical College, Binzhou 256603.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Heze Boai Hospital, Heze 274000.
authors.forename: Bin
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Jinan e-Join Science and Technology, Co., Ltd, Jinan 250100.
authors.forename: Yizhao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Shandong University Qilu Hospital, Jinan 250012, China.
authors.forename: Huaxiang
authors.initials: H
authors.lastname: Liu
keywords: Dideoxycytidine; Dorsal root ganglion; Insulin-like growth factor-1; Neuron; Neurotoxicity; gp120