Image analysis of neuritic regeneration by adult rat dorsal root ganglion neurons in culture: quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain-derived neurotrophic factor or neurotrophin-3.
Peripheral neuropathies are a common side effect of chemotherapeutic agents, particularly antineoplastic drugs such as taxol, cisplatin, or vinca-alkaloids (vincristine, vinblastine, vindesine). Using dissociated cultures of adult rat dorsal root ganglion (DRG) neurons and video image analysis after neurofilament immunostaining, we have designed a system that allows: (i) rapid screening of potential neurotoxic agents, with the establishment of dose-response curves and the calculation of IC50; (ii) quantification of neurotrophic effects; and (iii) demonstration of neuroprotection by trophic factors. In particular, we show that nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) stimulate in vitro neuritic regeneration by adult rat DRG neurons, while brain-derived neurotrophic factor and neurotrophin-3 lack such effects. Furthermore, 24 h of pretreatment by NGF or bFGF drastically decreases the neurotoxic effect of vincristine and cisplatin.
Malgrange
B
B
Department of Human Physiology and Pathophysiology, University of Liège, Belgium.
Delrée
P
P
Rigo
J M
JM
Baron
H
H
Moonen
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D019208:Brain-Derived Neurotrophic Factor; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D003078:Colchicine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure*; D016900:Neurofilament Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3; D017239:Paclitaxel / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014743:Videotape Recording; D014748:Vinca Alkaloids / Q000633:toxicity
D000970:Antineoplastic Agents; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D020933:Neurotrophin 3; D014748:Vinca Alkaloids; D016222:Fibroblast Growth Factor 2; D017239:Paclitaxel; D002945:Cisplatin; D003078:Colchicine