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Influence of leukemia inhibitory factor on galanin/GMAP and neuropeptide Y expression in mouse primary sensory neurons after axotomy

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Abstract

The effect of unilateral transection of the sciatic nerve on expression of immunoreactive galanin (GAL), galanin-message-associated peptide (GMAP) and neuropeptide tyrosine (NPY) in dorsal root ganglia (DRGs) was studied in wild-type mice and in leukemia inhibitory factor (LIF)-deficient mice. In normal and contralateral DRGs small numbers of weakly fluorescent GAL- and GMAP-positive neuronal cell bodies and numerous positive fibers were observed. No NPY-positive cell bodies but a few fibers surrounding blood vessels were seen. In LIF deficient mice hardly any GAL- or GMAP-positive neurons or fibers were seen, nor was NPY-like immunoreactivity present in cell bodies. After axotomy there was a dramatic upregulation of all three peptides in wild-type DRG neurons, whereby 50–60% of the neuron profiles, encompassing both small and large profiles, were GAL- and GMAP-immunoreactive (IR). About one third of all neuron profiles, mainly large ones, were NPY-positive. In LIF-deficient mice this upregulation was much less pronounced. Thus GAL- and GMAP-IR neuron profiles were reduced by 65–70% compared with the wild-type mice. The number of NPY-positive neuron profiles was reduced to half but this difference was not significant. There was also an ipsilateral decrease in fluorescence intensity for all three peptide immunoreactivities in the LIF-deficient mice as compared with wild-type mice after axotomy. There was no apparent difference in size between, respectively, GAL- and GMAP-positive profiles when comparing LIF-deficient and wild-type mice before or after axotomy. There were, however, no small NPY-IR profiles in the LIF-deficient group. The present results suggests that LIF is important for the dramatic upregulation of GAL and GMAP seen after axotomy. It may also be important for the normal expression of galanin in mouse DRGs, since wild-type mice seemed to have somewhat more positive cell bodies and more fluorescent fibers. LIF seems to be less important for the control of NPY synthesis, but may be involved in NPY regulation in small-sized neurons.

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References

  • Bamber BA, Masters BA, Hoyle GW, Brinster RL, Palmiter RD (1994) Leukemia inhibitory factor induces neurotransmitter switching in transgenic mice. Proc Natl Acad Sci USA 91: 7839–7843

    Google Scholar 

  • Banner LR, Patterson PH (1994) Major changes in the expression of the mRNAs for cholinergic differentiation factor/leukemia inhibitory factor and its receptor after injury to adult peripheral nerves and ganglia. Proc Natl Acad Sci USA 91: 7109–7113

    Google Scholar 

  • Coons AH (1958) Fluorescent antibody methods. In: Danielli JF (ed) General cytochemical methods. Academic Press, New York, pp 399–422

    Google Scholar 

  • Cortés R, Ceccatelli S, Schalling M, Hökfelt T (1990a) Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: an in situ hybridization study. Synapse 6: 369–391

    Google Scholar 

  • Cortés R, Villar MJ, Verhofstad A, Hökfelt T (1990b) Effects of central nervous system lesions on the expression of galanin: a comparative in situ hybridization and immunohistochemical study. Proc Natl Acad Sci USA 87: 7742–7746

    Google Scholar 

  • Escary J-L, Perreau J, Dumenil D, Ezine S, Brulet P (1993) Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation. Nature 363: 361–364

    Google Scholar 

  • Farkas-Szallasi T, Lundberg JM, Wiesenfeld-Hallin Z, Hökfelt T, Szallasi A (1995) Increased levels of GMAP, VIP and nitric oxide synthase, and their mRNAs, in lumbar dorsal root ganglia of the rat following systemic resiniferatoxin treatment. Neuroreport 6: 2230–2234

    Google Scholar 

  • Fitzgerald M, Wall PD, Goedert M, Emson PC (1985) Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section. Brain Res 332: 131–141

    Google Scholar 

  • Freidin M, Kessler JA (1991) Cytokine regulation of substance P expression in sympathetic neurons. Proc Natl Acad Sci USA 88: 3200–3203

    Google Scholar 

  • Fukada K (1985) Purification and partial characterization of a cholinergic neuronal differentiation factor. Proc Natl Acad Sci USA 82: 8795–8799

    Google Scholar 

  • Hiura A, Sakamoto Y (1987) Quantitative estimation of the effects of capsaicin on the mouse primary sensory neurons. Neurosci Lett 76: 101–106

    Google Scholar 

  • Hökfelt T, Wiesenfeld-Hallin Z, Villar MJ, Melander T (1987) Increase of galanin-like immunoreactivity in rat dorsal root ganglion cells after peripheral axotomy. Neurosci Lett 83: 217–220

    Google Scholar 

  • Hökfelt T, Åman K, Arvidsson U, Bedecs K, Ceccatelli S, Hulting A, Langel Ü, Meister B, Pieribone V, Bartfai T (1992) Galanin message-associated peptide (GMAP)and galanin-like immunoreactivities: overlapping and differential distributions in the rat. Neurosci Lett 142: 139–142

    Google Scholar 

  • Hökfelt T, Zhang X, Wiesenfeld-Hallin Z (1994) Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neurosci 17: 22–30

    Google Scholar 

  • Inaishi Y, Kashihara Y, Sakaguchi M, Nawa H, Kuno M (1992) Cooperative regulation of calcitonin gene-related peptide levels in rat sensory neurons via their central and peripheral processes. J Neurosci 12: 518–524

    Google Scholar 

  • Johnson DG, de C Nougueira Araujo GM (1981) A simple method of reducing the fading of immunofluorescence during microscopy. J Immunol Methods 43: 349–350

    Google Scholar 

  • Kashiba H, Senba E, Kawai Y, Ueda Y, Tohyama M (1992a) Axonal blockade induces the expression of vasoactive intestinal polypeptide and galanin in rat dorsal root ganglion neurons. Brain Res 577: 19–28

    Google Scholar 

  • Kashiba H, Senba E, Ueda Y, Tohyama M (1992b) Co-localized but target-unrelated expression of vasoactive intestinal polypeptide and galanin in rat dorsal root ganglion neurons after peripheral nerve crush injury. Brain Res 582: 47–57

    Google Scholar 

  • Kessler JA, Black IB (1980) Nerve growth factor stimulates the development of substance P in sensory ganglia. Proc Natl Acad Sci USA 77: 649–652

    Google Scholar 

  • Lindsay RM, Harmar AJ (1989) Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature 337: 362–364

    Google Scholar 

  • Lindsay RM, Lockett C, Sternberg J, Winter J (1989) Neuropeptide expression in cultures of adult sensory neurons: modulation of substance P and calcitonin gene-related peptide levels by nerve growth factor. Neuroscience 33: 53–65

    Google Scholar 

  • Mohney RP, Siegel RE, Zigmond RE (1994) Galanin and vasoactive intestinal peptide messenger RNAs increase following axotomy of adult sympathetic neurons. J Neurobiol 25: 108–118

    Google Scholar 

  • Mulderry PK (1994) Neuropeptide expression by newborn and adult rat sensory neurons in culture: effects of nerve growth factor and other neurotrophic factors. Neuroscience 59: 673–688

    Google Scholar 

  • Nawa H, Patterson PH (1990) Separation and partial characterization of neuropeptide-inducing factors in heart cell conditioned medium. Neuron 4: 269–277

    Google Scholar 

  • Nawa H, Nakanishi S, Patterson PH (1991) Recombinant cholinergic differentiation factor (leukemia inhibitory factor) regulates sympathetic neuron phenotype by alterations in the size and amounts of neuropeptide mRNAs. J Neurochem 56: 2147–2150

    Google Scholar 

  • Noguchi K, Senba E, Morita Y, Sato M, Tohyama M (1989) Prepro-VIP and preprotachykinin mRNAs in the rat dorsal root ganglion cells following peripheral axotomy. Mol Brain Res 6: 327–330

    Google Scholar 

  • Noguchi K, De Leon M, Nahin RL, Senba E, Ruda MA (1994) Quantification of axotomy-induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment. J Neurosci 35: 54–66

    Google Scholar 

  • Otten U, Goedert M, Mayer N, Lembeck F (1980) Requirement of nerve growth factor for development of substance P-containing sensory neurons. Nature 287: 158–159

    Google Scholar 

  • Patterson PH (1994) Leukemia inhibitory factor, a cytokine at the interface between neurobiology and immunology. Proc Natl Acad Sci USA 91: 7833–7835

    Google Scholar 

  • Patterson PH, Nawa H (1993) Neuronal differentiation factors/cytokines and synaptic plasticity. Cell 10: 123–137

    Google Scholar 

  • Platt JL, Michael AF (1983) Retardation of fading and enhancement of intensity of immunofluorescence by para-phenylenediamine. J Histochem Cytochem 31: 840–842

    Google Scholar 

  • Rao MS, Tyrrell S, Landis SC, Patterson PH (1992) Effect of ciliary neurotrophic factor (CNTF) and depolarization on neuropeptide expression in cultured sympathetic neurons. Dev Biol 150: 281–293

    Google Scholar 

  • Rao MS, Sun Y, Escary JL, Perreau J, Tresser S, Patterson PH, Zigmond RE, Brulet P, Landis SC (1993) Leukemia inhibitory factor mediates an injury response but not a target-directed developmental transmitter switch in sympathetic neurons. Neuron 11: 1175–1185

    Google Scholar 

  • Rökaeus Å, Brownstein MJ (1986) Construction of a porcine adrenal medullary cDNA library and nucleotide sequence analysis of two clones encoding a galanin precursor. Proc Natl Acad Sci USA 83: 6287–6291

    Google Scholar 

  • Schreiber RC, Hyatt SH, Bennett TA, Zigmond RE (1994) Galanin expression increases in adult rat sympathetic neurons after axotomy. Neuroscience 60: 17–27

    Google Scholar 

  • Shadiack AM, Hart RP, Carlson C, Jonakait GM (1993) Interleukin-1 induces substance P in sympathetic ganglia through the induction of leukemia inhibitory factor. J Neurosci 13: 2601–2609

    Google Scholar 

  • Shehab SA, Atkinson ME (1986) Vasoactive intestinal polypeptide (VIP) increases in the spinal cord after peripheral axotomy of the sciatic nerve originate from primary afferent neurons. Brain Res 372: 37–44

    Google Scholar 

  • Verge VMK, Richardson PM, Wisenfeld-Hallin Z, Hökfelt T (1995) Differential influence of nerve growth factor on neuropeptide expression in vivo: a novel role in peptide suppression in adult sensory neurons. J Neurosci 15: 2081–2096

    Google Scholar 

  • Villar MJ, Cortés R, Theodorsson E, Wiesenfeld-Hallin Z, Schalling M, Fahrenkrug J, Emson PC, Hökfelt T (1989) Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin. Neuroscience 33: 587–604

    Google Scholar 

  • Villar MJ, Meister B, Cortés R, Schalling M, Morris M, Hökfelt T (1990) Neuropeptide gene expression in hypothalamic magnocellular neurons of normal and hypophysectomized rats: a combined immunohistochemical and in situ hybridization study. Neuroscience 36: 181–199

    Google Scholar 

  • Villar MJ, Wiesenfeld-Hallin Z, Xu XJ, Theodorsson E, Emson PC, Hökfelt T (1991) Further studies on galanin-, substance P-, and CGRP-like immunoreactivities in primary sensory neurons and spinal cord: effects of dorsal rhizotomies and sciatic nerve lesions. Exp Neurol 112: 29–39

    Google Scholar 

  • Vrontakis ME, Peden LM, Duckworth ML, Friesen HG (1987) Isolation and characterization of a complementary DNA (galanin) clone from estrogen-induced pituitary tumor messenger MNA. J Biol Chem 262: 16755–16758

    Google Scholar 

  • Wakisaka S, Kajander KC, Bennett GJ (1991) Increased neuropeptide Y (NPY)-like immunoreactivity in rat sensory neurons following peripheral axotomy. Neurosci Lett 124: 200–203

    Google Scholar 

  • Wakisaka S, Kajander KC, Bennett GJ (1992) Effects of peripheral nerve injuries and tissue inflammation on the levels of neuropeptide Y-like immunoreactivity in rat primary afferent neurons. Brain Res 598: 349–352

    Google Scholar 

  • Willis WDJ, Coggeshall RE (1991) Sensory mechanisms of the spinal cord. Plenum Press, New York

    Google Scholar 

  • Xu X-J, Andell S, Zhang X, Wiesenfeld-Hallin Z, Langel Ü, Bedecs K, Hökfelt T, Bartfai T (1995) Peripheral axotomy increases the expression of galanin message-associated peptide (GMAP) in dorsal root ganglion cells and alters the effects of intrathecal GMAP on the flexor reflex in the rat. Neuropeptides 28: 299–307

    Google Scholar 

  • Yamamori T, Fukada K, Aebersold R, Korsching S, Fann MJ, Patterson PH (1989) The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science 246: 1412–1416

    Google Scholar 

  • Zamboni I, De Martino C (1967) Buffered picric acid formaldehyde: a new rapid fixative for electron microscopy. J Cell Biol 35:148A

    Google Scholar 

  • Zhang Q, Ji R-R, Lindsay R, Hökfelt T (1995a) Effect of growth factors on substance P mRNA expression in axotomized dorsal root ganglia. Neuroreport 6: 1309–1312

    Google Scholar 

  • Zhang Q, Shi T-J, Ji R-R, Zhang Y-T, Sundler F, Hannibal J, Fahrenkrug J, Hökfelt T (1995b) Expression of pituitary adenylate cyclase-activating polypeptide in dorsal root ganglia following axotomy: time course and coexistence. Brain Res 705: 149–158

    Google Scholar 

  • Zhang X, Meister B, Elde R, Verge VMK, Terenius L, Hökfelt T (1993) Large caliber primary afferent neurons projecting to the gracile nucleus express neuropeptide Y after sciatic nerve lesions: an immunohistochemical and in situ hybridization study in rats. Eur J Neurosci 5: 1510–1519

    Google Scholar 

  • Zhang X, Dagerlind Å, Bao L, Ji RR, Lundberg M, Hökfelt T (1994) Increased expression of galanin in the rat superior cervical ganglion after pre- and postganglionic nerve lesions. Exp Neurol 127: 9–22

    Google Scholar 

  • Zhang X, Bean AJ, Wiesenfeld-Hallin Z, Xu X-J, Hökfelt T (1995) Ultrastractural studies on peptides in the dorsal horn of the rat spinal cord. III. Effects of peripheral axotomy with special reference to galanin. Neuroscience 64: 893–915

    Google Scholar 

  • Zhang YZ, Hannibal J, Zhao Q, Moller K, Danielsen N, Fahrenkrug J, Sundler F (1996) Pituitary adenylate cyclase activating peptide (PACAP) expression in the rat dorsal root ganglia: up-regulation after peripheral nerve injury. Neuroscience (in press)

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Corness, J., Shi, TJ., Xu, ZQ. et al. Influence of leukemia inhibitory factor on galanin/GMAP and neuropeptide Y expression in mouse primary sensory neurons after axotomy. Exp Brain Res 112, 79–88 (1996). https://doi.org/10.1007/BF00227180

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