Biomol Ther.  2014 Nov;22(6):532-539. 10.4062/biomolther.2014.036.

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro

• Lu L
• Dong H
• Liu G
• Yuan B
• Li Y
• Liu H

• KMID: 2170595
• DOI: http://doi.org/10.4062/biomolther.2014.036

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 micromol/L), gp120 (500 pmol/L) plus ddC (50 micromol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 micromol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 micromol/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 microm), whereas ddC mainly affected small diameter DRG neurons (< or =25 microm). 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.

Keyword

gp120; Dideoxycytidine; Neurotoxicity; Insulin-like growth factor-1; Neuron; Dorsal root ganglion

MeSH Terms

Analgesics
Animals
Diagnosis-Related Groups*
Ganglia, Spinal
HIV
Humans
Insulin-Like Growth Factor I*
Neuralgia
Neurons*
Peripheral Nervous System Diseases
Rats
Zalcitabine*
Analgesics
Insulin-Like Growth Factor I
Zalcitabine