Contribution of neurotrophin-3 to the neuropeptide Y-induced increase in neurite outgrowth of rat dorsal root ganglion cells.
Recent studies show that neuropeptide Y acts indirectly, via release of a neurotrophic factor(s) from the spinal cord, to increase the neurite outgrowth of dissociated adult rat dorsal root ganglion cells. This study examines further the neuropeptide Y-induced increase in neurite outgrowth. To characterize the factor(s) mediating the neuropeptide Y-induced increase in neurite outgrowth, we have examined whether antisera to either nerve growth factor or neurotrophin-3 influence the neuropeptide Y-induced increase in neurite outgrowth. Spinal cord slices were incubated with media alone or in combination with 10 nM neuropeptide Y for 2 h at 37 degrees C. The supernatant of spinal cord incubated with neuropeptide Y significantly enhanced the neurite outgrowth of normal dorsal root ganglion cells. Antiserum against nerve growth factor had no effect on the trophic actions of the supernatant. Antiserum against neurotrophin-3, however, significantly attenuated the increase in neurite outgrowth. Consistent with this finding, neurotrophin-3 also increased the percentage of cells with neurites. Transganglionic labelling of A-fibres with choleragenoid-horseradish peroxidase in animals treated intrathecally with neurotrophin-3 for 14 days via an osmotic pump showed that the area of choleragenoid-horseradish peroxidase label expanded into lamina II. In comparison, saline-treated animals had no label in lamina II. In addition, neurotrophin-3-treated animals also had a significant decrease in mechanical nociceptive threshold. The results suggest that neuropeptide Y acts via neurotrophin-3 to mediate an increase in neurite outgrowth of dorsal root ganglion cells. These results have important implications for the mechanisms underlying neuropathic pain.
White
D M
DM
Department of Anaesthesia and Pain Management, University of Sydney, NSW, Australia.
D000818:Animals; D000906:Antibodies; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005727:Ganglia, Spinal / Q000166:cytology* / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009478:Neuropeptide Y / Q000494:pharmacology / Q000502:physiology*; D020933:Neurotrophin 3; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000502:physiology*; D013997:Time Factors
D000906:Antibodies; D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D020933:Neurotrophin 3