Merck
  • Dorsal root ganglion explants derived from chemotherapy-treated mice have reduced neurite outgrowth in culture.

Dorsal root ganglion explants derived from chemotherapy-treated mice have reduced neurite outgrowth in culture.

Neuroscience letters (2018-11-16)
Lital Livni, Justin G Lees, Mallory E Barkl-Luke, David Goldstein, Gila Moalem-Taylor
ABSTRACT

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and debilitating adverse effect of cancer therapy that results from treatment with neurotoxic agents. Although chemotherapy treatment has been shown to inhibit neurite outgrowth from dorsal root ganglion (DRG) neurons in vitro, evidence for this effect in vivo is lacking. In this study, we investigated whether chemotherapy treatment in mice alters the capacity for axonal outgrowth from ex vivo cultured DRG explants. Using a neurite outgrowth assay, we demonstrated that DRG explants isolated at day 30 from mice treated with 6 cycles of paclitaxel, or 12 cycles of oxaliplatin showed a significant reduction in neurite outgrowth as compared to DRG explants from control vehicle-treated mice. DRGs that were isolated at day 90 showed recovery of the neurite outgrowth, and no significant differences were detected in comparison to vehicle controls. These results are corroborated with an in vitro model, whereby direct application of oxaliplatin and paclitaxel dose-dependently reduced neurite outgrowth of DRG explants. In conclusion, our results show that the effect of paclitaxel and oxaliplatin on the structural plasticity of DRG is retained ex vivo (for at least 30 days) and suggest the use of DRG explants derived from chemotherapy-treated mice as an efficient method to investigate the mechanisms underlying CIPN and test for possible therapeutic targets.