Pharmacological evaluation of rat dorsal root ganglion neurons as an in vitro model for diabetic neuropathy

Abstract

Eve Peeraer1,2, An Van Lutsenborg3, An Verheyen1,4, Raf De Jongh5, Rony Nuydens1, Theo F Meert1,21Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium; 2University Hasselt, Hasselt, Belgium; 3Free University Brussels, Brussels, Belgium; 4The Vesalius Research Center, University of Leuven, Leuven, Belgium; 5Intensive Care and Emergency Care, Ziekenhuis Oost-Limburg, Genk, BelgiumBackground: Diabetic neuropathy is a complication of diabetes mellitus that develops in about 50% of people with diabetes. Despite its widespread occurrence and devastating effects, this complication is still not fully understood, and there is no treatment available to prevent its development.Methods: In this study, immunocytochemistry for activating transcription factor 3, a marker for cell injury, was used to investigate the stress response in dorsal root ganglion neurons in both in vitro and ex vivo models of diabetic neuropathy.Results: Our findings showed increased activating transcription factor 3 expression in hyperglycemic culture conditions and in dorsal root ganglion neurons isolated from diabetic rats. Glial cell line-derived neurotrophic factor, a substance with known neuroprotective properties, was able to reduce diabetes mellitus-induced neuronal stress in vitro, while gabapentin and carbamazepine, currently used to treat neuropathic pain, showed only limited effects.Conclusion: Growth factors may have a therapeutic benefit as neurotrophic agents in the treatment of diabetic peripheral neuropathy, but gabapentin and carbamazepine have no direct protective effect on sensory neurons. This research also indicates that immunocytochemistry for activating transcription factor 3 is a valuable tool for evaluation of pharmacological substances in dorsal root ganglion cultures.Keywords: diabetic peripheral neuropathy, dorsal root ganglion, activating transcription factor 3, glial cell line-derived neurotrophic factor, anticonvulsants