Neuropeptide expression by newborn and adult rat sensory neurons in culture: effects of nerve growth factor and other neurotrophic factors.
Adult rat dorsal root ganglion sensory neurons in culture require nerve growth factor for synthesis of substance P and calcitonin gene-related peptide but express vasoactive intestinal peptide independently of nerve growth factor. In contrast, the same neurons from newborn rats do not express detectable vasoactive intestinal polypeptide when cultured with nerve growth factor. To further explore the mechanisms regulating neuropeptide expression in these cells, I compared the effects of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, ciliary neurotrophic factor and leukaemia inhibitory factor on substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and somatostatin expression in rat dorsal root ganglion cultures. As with neurons from adult animals, newborn rat sensory neurons required nerve growth factor for synthesis of substance P and calcitonin gene-related peptide. This effect was independent of neuronal survival since most neurons capable of expressing these peptides appeared to survive without added neurotrophic factors. Neurons surviving in the absence of nerve growth factor also expressed vasoactive intestinal polypeptide, suggesting that nerve growth factor suppresses vasoactive intestinal polypeptide expression in immature neurons. However, nerve growth factor withdrawal after eight days' culture failed to cause vasoactive intestinal polypeptide induction which therefore appears to depend on other factors also. Neither ciliary neurotrophic factor nor leukaemia inhibitory factor affected peptide levels when used alone, but both inhibited nerve growth factor-stimulated expression of substance P and calcitonin gene-related peptide in adult rat neurons. They also stimulated vasoactive intestinal polypeptide expression in newborn rat neurons in the presence of nerve growth factor but not to such high levels as those seen under conditions of nerve growth factor deprivation. Neither brain-derived neurotrophic factor nor neurotrophin-3 affected peptide expression significantly. Somatostatin was defected in adult rat neurons, but was unaffected by neurotrophic factors. No somatostatin was detected in newborn rat neurons. These results suggest that in immature animals at least, the increased expression of vasoactive intestinal polypeptide seen in sensory neurons following peripheral nerve injury in vivo, could result from deprivation of target-derived nerve growth factor in combination with increased availability of ciliary neurotrophic factor or leukaemia inhibitory factor from the injured nerve.
Mulderry
P K
PK
MRC Brain Metabolism Unit, Royal Edinburgh Hospital, U.K.
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005727:Ganglia, Spinal / Q000254:growth & development / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D015850:Interleukin-6; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis*; D020933:Neurotrophin 3; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000096:biosynthesis; D013373:Substance P / Q000096:biosynthesis; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D020933:Neurotrophin 3; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide