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.
Department of Anaesthesia and Pain Management, University of Sydney, NSW, Australia.
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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