NO-cGMP mediated galanin expression in NGF-deprived or axotomized sensory neurons

• Published in: Journal of neurochemistry Vol. 100; no. 3; pp. 790 - 801
• Main Authors: Thippeswamy, Thimmasettappa, Haddley, Kate, Corness, Jacquie D, Howard, Mark R, McKay, Jennifer S, Beaucourt, Stephanie M, Pope, Marion D, Murphy, David, Morris, Richard, Hökfelt, Tomas, Quinn, John P
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-02-2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Animals; Axotomy; Biological and medical sciences; Cell Survival - drug effects; Cell Survival - genetics; Cells, Cultured; Cyclic GMP - metabolism; dorsal root ganglion neuron; Enzymes; Fundamental and applied biological sciences. Psychology; galanin; Galanin - metabolism; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Gene expression; Gene Expression Regulation - genetics; Genes, Reporter - genetics; Genetic Vectors - genetics; Hematologic and hematopoietic diseases; leukaemia inhibitory factor; Leukemia; Leukemia Inhibitory Factor - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Knockout; nerve growth factor; Nerve Growth Factor - deficiency; Nerve Regeneration - drug effects; Nerve Regeneration - genetics; Neurons; Neurons, Afferent - cytology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Promoter Regions, Genetic - genetics; Rats; Rats, Wistar; Rodents; Sciatic Neuropathy - genetics; Sciatic Neuropathy - metabolism; Sciatic Neuropathy - physiopathology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs; Spinal cord; Rat; Leukemia; Central nervous system; Phosphorus-oxygen lyases; leukaemia inhibitory factor; Nerve growth factor; Lyases; Synthase; Guanylate cyclase; Endogenous; Vector; galanin; Enzyme; Luciferase; Rodentia; Malignant hemopathy; axotomy; Gene expression; In vitro; Survival; Infection; Vertebrata; Mammalia; Mouse; Nitric oxide; dorsal root ganglion neuron; Sensory neuron; Spinal ganglion; Oxidoreductases
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04243.x

Leukaemia inhibitory factor (LIF) and nerve growth factor (NGF) are well characterized regulators of galanin expression. However, LIF knockout mice containing the rat galanin 5' proximal promoter fragment (- 2546 to + 15 bp) driving luciferase responded to axotomy in the same way as control mice. Also, LIF had no effect on reporter gene expression in vitro, neither in the presence or absence of NGF, suggesting that other factors mediate an axotomy response from the galanin promoter. We then addressed the role of nitric oxide (NO) using NGF-deprived rat dorsal root ganglion (DRG) neuron cultures infected with viral vectors containing the above-mentioned construct, and also studied endogenous galanin expression in axotomized DRG in vivo. Blocking endogenous NO in NGF-deprived DRG cultures suppressed galanin promoter activity. Consistent with this, axotomized/NGF-deprived DRG neurons expressed high levels of neuronal NO synthase (nNOS) and galanin. Further, using pharmacological NOS blockers, or adenoviral vectors expressing dominant-negative either for nNOS or soluble guanylate cyclase in vivo and in vitro, we show that the NO-cGMP pathway induces endogenous galanin in DRG neurons. We propose that both LIF and NO, acting at different promoter regions, are important for the up-regulation of galanin, and for DRG neuron survival and regeneration after axotomy.