Background: HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated
sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity
are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms
caused by gp120-induced neurotoxicity.
Methods: In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root
ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive
DRG neurons with gp120-induced neurotoxicity were also determined.
Results: The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited
neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons
from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA
and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation
with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.
Conclusion: These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of
DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity.
These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential
therapeutic effects of IGF-1 on gp120-induced neurotoxicity.