Glucocorticoid effects on Fos immunoreactivity and NADPH-diaphorase histochemical staining following spinal cord injury
Glucocorticoids (GC) provide neuroprotection and early recovery after spinal cord injury (SCI). While several mechanisms were proposed to account for these effects, limited information exists regarding GC actions in sensory areas of the spinal cord. Presently, we studied the time course of Fos expre...
Guardado en:
| Autor principal: | |
|---|---|
| Otros Autores: | , , , , |
| Formato: | Capítulo de libro |
| Lenguaje: | Inglés |
| Publicado: |
2001
|
| Acceso en línea: | Registro en Scopus DOI Handle Registro en la Biblioteca Digital |
| Aporte de: | Registro referencial: Solicitar el recurso aquí |
| Sumario: | Glucocorticoids (GC) provide neuroprotection and early recovery after spinal cord injury (SCI). While several mechanisms were proposed to account for these effects, limited information exists regarding GC actions in sensory areas of the spinal cord. Presently, we studied the time course of Fos expression, and reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical staining to monitor neuronal responses to SCI with or without GC treatment. Rats with sham-operation or transection at the thoracic level (T7-T8) received vehicle or 5 mg/kg of the GC dexamethasone (DEX) at 5 min post-lesion and were sacrificed 2 or 4 h after surgery. Another group of SCI rats received vehicle or intensive DEX treatment (5 min, 6 h, 18 h and 46 h post-lesion) and were sacrificed 48 h after surgery. The number of NADPH-d positive neurons or Fos immunoreactive nuclei was studied by computer-assisted image analysis in superficial dorsal horn (Laminae I-III) and central canal area (Lamina X) below the lesion. While constitutive Fos immunoreactive nuclei were sparse in controls, SCI increased Fos expression at 2 and 4 h after injury. DEX treatment significantly enhanced the number of Fos positive nuclei in Laminae I-III by 4 h after transection, although the response was not maintained by intensive steroid treatment when tested at 48 h after SCI. NADPH-d positive neurons in Laminae I-III increased at 2 and 4 h after SCI while a delayed increased was found in central canal area (Lamina X). DEX treatment decreased NADPH-d positive neurons to sham-operated levels at all time points examined. Thus, while GC stimulation of Fos suggests activation of neurons involved in sympathetic outflow and/or pain, down-regulation of NADPH-d indicates attenuation of nociceptive outflow, considering the role of enzyme-derived nitric oxide in pain-related mechanisms. Differential hormonal effects on these molecules agree with their localization in different cell populations. © 2001 Elsevier Science B.V. All rights reserved. |
|---|---|
| Bibliografía: | Bartholdi, D., Schwab, M.E., Methylprednisolone inhibits early inflammatory processes but not ischemic cell death after experimental spinal cord lesion in the rat (1995) Brain Res., 672, pp. 177-186 Bethea, J.R., Castro, M., Keane, R.W., Lee, T.T., Dietrich, W.D., Yezierski, R.P., Traumatic spinal cord injury induces nuclear factor-kB activation (1998) J. Neurosci., 18, pp. 3251-3260 Bracken, M.B., Shepard, M.J., Collins, W.F., Holford, T.R., Baskin, D.S., Eisenberg, H.M., Flamm, E., Winn, H.R., A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury (1990) New England J. Med., 322, pp. 1405-1411 Brandoli, C., Shi, B., Pflug, B., Andrews, P., Wrathall, J.R., Mochetti, I.I., Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord (2001) Mol. Brain Res., 19, pp. 61-70 Braughler, J.M., Hall, E.D., Correlation of methylprednisolone levels in cat spinal cord with its effects on (Na, K-)ATPase, lipid peroxidation and alpha motor neuron function (1982) J. Neurosurg., 56, pp. 838-844 Briski, K.P., DiPasquale, B.M., Gillen, E., Induction of immediate-early genes in preoptic and hypothalamic neurons by the glucocorticoid receptor agonist, dexamethasone (1997) Brain Res., 768, pp. 185-196 Buritova, J., Honore, P., Chapman, V., Besson, J.M., Enhanced effect of co-administered dexamethasone and diclofenac on inflammatory pain processing and associated spinal c-fos expression in the rat (1996) Pain, 64, pp. 559-568 Callsen-Cencic, P., Hoheisel, U., Kaske, A., Mense, S., Tenschert, S., The controversy about spinal neuronal nitric oxide synthase: Under which conditions is it up- or downregulated? (1999) Tissue Res., 295, pp. 183-194 Chen, A., Xu, X.M., Kleitman, N., Bunge, M.B., Methylprednisolone administration improves axonal regeneration into Schwann cell grafts in transacted adult rat thoracic spinal cord (1996) Exp. Neurol., 138, pp. 261-276 Cintra, A., Molander, C., Fuxe, K., Colocalization of Fos and glucocorticoid receptor-immunoreactivities is present only in a very restricted population of dorsal horn neurons of the rat spinal cord after nociceptive stimulation (1993) Brain Res., 632, pp. 334-338 De Nicola, A.F., Steroid hormones and neuronal regeneration (1993) Adv. Neurol., 59, pp. 199-206 Dubner, R., Ruda, M.A., Activity-dependent neuronal plasticity following tissue injury and inflammation (1992) Trends Neurosci., 15, pp. 96-103 Duncan, G.E., Stumpf, W.E., Target neurons for (3H)-corticosterone in the rat spinal cord (1984) Brain Res., 307, pp. 321-326 Ferreira, S.H., Cunha, F.Q., Lorenzetti, B.B., Michelin, M.A., Perretti, M., Flower, R.J., Poole, S., Role of lipocortin-1 in the anti-hyperalgesic actions of dexamethasone (1997) Br. J. Pharmacol., 121, pp. 883-888 Ferrini, M., Gonzalez, S., Antakly, T., De Nicola, A.F., Immunocytochemical localization of glucocorticoid receptors in the spinal cord: Effects of adrenalectomy, glucocorticoid treatment, and spinal cord transection (1993) Cell. Mol. Neurobiol., 13, pp. 387-397 Ferrini, M., Piroli, G., Frontera, M., Falbo, A., Lima, A., De Nicola, A.F., Estrogens normalize the hypothalamic-pituitary-adrenal axis response to stress and increase glucocorticoid receptor immunoreactivity in hippocampus of aging male rats (1999) Neuroendocrinology, 69, pp. 129-137 Fürst, S., Transmitters involved in antinociception in the spinal cord (1999) Brain Res. Bull., 48, pp. 129-141 Fuxe, K., Harfstrand, A., Agnati, L.F., Yu, Z.-Y., Cintra, A., Wikstrom, A.C., Okret, S., Gustafsson, J.-A., Immunocytochemical studies on the localization of glucocorticoid receptor immunoreactive cells in the lower brain stem and spinal cord of the male rat using a monoclonal antibody against rat liver glucocorticoid receptor (1985) Neurosci. Lett., 60, pp. 1-6 Gonzalez, S., Moses, D.F., De Nicola, A.F., Glucocorticoid receptors and enzyme induction in the spinal cord of rats: Effects of acute transection (1990) J. Neurochem., 54, pp. 834-840 Gonzalez, S., Ferrini, M., Coirini, H., Gonzalez Deniselle, M.C., De Nicola, A.F., Regulation of flunitrazepam binding in the dorsal horn of the spinal cord by adrenalectomy and corticosteroids (1992) Brain Res., 589, pp. 97-101 González, S.L., Coirini, H., González Deniselle, M.C., González, S., Calandra, R., De Nicola, A.F., Time-dependent effects of dexamethasone on glutamate binding, ornithine decarboxylase activity and polyamine levels in the transected spinal cord (1995) J. Steroid Biochem. Mol. Biol., 55, pp. 85-92 González, S.L., Grillo, C., González Deniselle, M.C., Lima, A., McEwen, B.S., De Nicola, A.F., Dexamethasone up-regulates mRNA for Na, K-ATPase in some spinal cord neurons after cord transection (1996) Neuroreport, 7, pp. 1041-1044 González, S.L., Saravia, F., González Deniselle, M.C., Lima, A., De Nicola, A.F., Glucocorticoid regulation of motoneuronal parameters in rats with spinal cord injury (1999) Cell. Mol. Neurobiol., 19, pp. 597-611 González, S.L., González Deniselle, M.C., Lima, A., Guennoun, R., De Nicola, A.F., Glucocorticoid regulation of Fos-like immunoreactivity in the normal and injured spinal cord (2000) Society for Neuroscience 30th Annual Meeting, p. 510. , New Orleans, LA, USA González Deniselle, M.C., González, S.L., Lima, A., Wilkin, G., De Nicola, A.F., The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NADPH-diaphorase in the spinal cord of Wobbler mouse, a model for amyotrophic lateral sclerosis (1999) Neurochem. Res., 24, pp. 1-8 Gootman, O.M., Cohen, M.I., Sympathetic rhythms in spinal cats (1981) J. Auton. Nerv. Syst., 3, pp. 379-387 Hall, E.D., The neuroprotective pharmacology of methylprednisolone (1992) J. Neurosurg., 76, pp. 13-22 Hall, E.D., Neuroprotective actions of glucocorticoid and nonglucocorticoid steroids in acute neuronal injury (1993) Cell. Mol. Neurobiol., 13, pp. 415-432 Harris, J.A., Using c-fos as a neuronal marker of pain (1998) Brain Res. Bull., 45, pp. 1-8 Hughes, P., Dragunow, M., Induction of immediate early genes and the control of neurotransmitter-regulated gene expression within the nervous system (1995) Pharmacol. Rev., 47, pp. 133-178 Hunt, S.P., Pini, A., Evan, G., Induction of c-fos-like protein in spinal cord neurons following sensory stimulation (1987) Nature, 328, pp. 632-634 Kovács, K., c-Fos as a transcription factor: A stressful (re)view from a functional map (1998) Neurochem. Int., 33, pp. 287-297 Labombarda, F., Gonzalez, S.L., Roig, P., Lima, A., Guennoun, R., Schumacher, M., De Nicola, A.F., Modulation of NADPH-diaphorase and glial fibrillary acidic protein by progesterone in astrocytes from normal and injured rat spinal cord (2000) J. Steroid Biochem. Mol. Biol., 73, pp. 159-169 Lee, J.H., Price, R.H., Williams, F.G., Mayer, B., Beitz, A.J., Nitric oxide synthase is found in some spinothalamic neurons and in neuronal processes that appose spinal neurons that express Fos induced by noxious stimulation (1993) Brain Res., 608, pp. 324-333 Lopez Figueroa, M.O., Itoi, K., Watson, S.J., Regulation of nitric oxide synthase messenger RNA expression in the rat hippocampus by glucocorticoids (1998) Neuroscience, 87, pp. 439-446 Luo, L.G., Jackson, I.M.D., Glucocorticoids stimulate TRH and c-fos/c-jun gene expression in cultured hypothalamic neurons (1998) Brain Res., 791, pp. 56-62 Marlier, L.N.J.L., Csikos, T., Rebaudengo, N., Borboni, P., Patacchioli, F.R., Angelucci, L., Privat, A., Lauro, R., Distribution of glucocorticoid receptor mRNA in the rat spinal cord (1995) Neuroreport, 6, pp. 2245-2249 Marsala, J., Marsala, M., Vanicky, I., Taira, Y., Localization of NADPHd-exhibing neurons in the spinal cord of the rabbit (1999) J. Comp. Neurol., 406, pp. 263-284 Meller, S.T., Gebhart, G.F., Nitric oxide (NO) and nociceptive processing in the spinal cord (1993) Pain, 52, pp. 127-136 Molander, C., Xu, Q., Grant, G., The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord (1984) J. Comp. Neurol., 230, pp. 133-141 Nahin, R.L., Madsen, A.M., Giesler, G.J., Anatomical and physiological studies of the gray matter surrounding the spinal cord central canal (1983) J. Comp. Neurol., 220, pp. 321-335 Nicholas, A.P., Zhang, X., Hökfelt, T., An immunocytochemical investigation of the opioid cell column in lamina X of the male rat lumbosacral spinal cord (1999) Neurosci. Lett., 270, pp. 9-12 Nohr, D., Schafer, M.K., Persson, S., Romeo, H., Nyberg, F., Post, C., Ekstrom, G., Weihe, G.E., Calcitonin gene-related peptide gene expression in collagen induced arthritis is differentially regulated in primary afferents and motoneurons: Influence of glucocorticoids (1999) Neuroscience, 93, pp. 759-773 Orendácová, J., Marsala, M., Sulla, I., Kafka, J., Jalc, P., Cizková, D., Taira, Y., Marsala, J., Incipient cauda equina syndrome as a model of somatovisceral pain dogs: Spinal cord structures involved as revealed by the expression of c-fos and NADPH-diaphorase activity (2000) Neuroscience, 95, pp. 543-557 Orti, E., Moses, D.F., Grillo, C., De Nicola, A.F., Glucocorticoid regulation of glycerolphosphate dehydrogenase and ornithine decarboxylase activities in the spinal cord of the rat (1987) J. Neurochem., 48, pp. 425-431 Oudega, M., Vargas, C.G., Weber, A.B., Kleitman, N., Bunge, M.B., Long-term effects of methylprednisolone following transection of adult rat spinal cord (1999) Eur. J. Neurosci., 11, pp. 2453-2464 Pehl, U., Schmidt, H.A., Electrophysiological responses of neurons in the rat spinal cord to nitric oxide (1997) Neuroscience, 77, pp. 563-573 Poree, L.R., Schramm, L.P., Role of cervical neurons in propriospinal inhibition of thoracic dorsal horn neurons (1992) Brain Res., 599, pp. 302-308 Radomski, M.W., Palmer, R.M.J., Moncada, S., Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells (1990) Proc. Natl. Acad. Sci., 87, pp. 10043-10047 Rodella, L., Rezzani, R., Agostini, C., Bianchi, R., Expression of NADPH-diaphorase and colocalization with Fos in the brain neurons of the rat following visceral noxius stimulation (1999) Brain Res., 834, pp. 173-177 Ruda, M.A., Besse, D., Inagaki, S., Deleón, M., Ren, K., Nitric oxide expression and regulation in the dorsal root ganglion and spinal cord (1994) Ann. NY Acad. Sci., 738, pp. 181-190 Ruggiero, D.A., Anwar, M., Kim, J., Sica, A.L., Gootman, N., Gootman, P.M., Induction of c-fos gene expression by spinal cord transection in the rat (1997) Brain Res., 763, pp. 21-29 Salt, T.E., Herring, P.L., Excitatory amino acid transmitter function in mammalian central pathways (1991) Excitatory Amino Acids and Synaptic Transmission, pp. 155-167. , H.V. Wheal, A.M. Thomson (Eds.), Academic Press, New York Sandkuhler, J., Treier, A.C., Liu, X.G., Ohnimus, M., The massive expression of c-Fos protein in spinal cord dorsal horn neurons is not followed by long-term changes in spinal nociception (1996) Neuroscience, 73, pp. 657-666 Saravia, F., Grillo, C., Ferrini, M., Roig, P., Lima, A., De Kloet, E.R., De Nicola, A.F., Changes of hypothalamic and plasma vasopressin in rats with deoxycorticosterone-acetate induced salt appetite (1999) J. Steroid Biochem. Mol. Biol., 70, pp. 47-57 Schwarz, P.M., Gierten, B., Boissel, J.-P., Forstermann, U., Expressional down-regulation of neuronal type nitric oxide synthase I by glucocorticoids in N1E-115 neuroblastoma cells (1998) Mol. Pharmacol., 54, pp. 258-263 Thao, Y.-X., Zhao, Z.Q., NMDA receptors mediating Fos expression in rat spinal cord induced by subcutaneous injection of formalin (1998) Acta Pharmacol. Sinica, 19, pp. 506-509 Traub, R.J., Solodkin, A., Gebhart, G.F., NADPH-diaphorase histochemistry provides evidence for a bilateral, somatotopically inappropriate response to unilateral hindpaw inflammation in the rat (1994) Brain Res., 647, pp. 113-123 Traub, R.J., Solodkin, A., Meller, S.T., Gebhart, G.F., Spinal cord NADPH-diaphorase histochemical staining but not nitric oxide synthase immunoreactivity increases following carrageenan-produced hindpaw inflammation in the rat (1994) Brain Res., 668, pp. 204-210 Urban, L., Thompson, S.W.N., Dray, A., Modulation of spinal excitability: Co-operation between neurokinins and excitatory amino acids neurotransmitters (1994) TINS, 17, pp. 432-438 Vincent, S.R., Kimura, H., Histochemical mapping of nitric oxide synthase in the rat brain (1992) Neuroscience, 46, pp. 755-784 Weber, C.M., Eke, B.C., Maines, M.D., Corticosterone regulates heme oxygenase-2 and NO synthase transcription and protein expression in rat brain (1994) J. Neurochem., 63, pp. 953-962 Wissink, S., Van Heerde, E.C., Van den Burg, B., Van der Saag, P.T., A dual mechanism mediates repression of NF-kB activity by glucocorticoids (1998) Mol. Endocrinol., 12, pp. 355-363 Wu, W., Li, Y., Schinco, F.P., Expression of c-jun and neuronal nitric oxide synthase in rat spinal motoneurons following axonal injury (1994) Neurosci. Lett., 179, pp. 157-181 Yan, P., Xu, J., Li, Q., Chen, S., Kim, G.M., Hsu, C.Y., Xu, X.M., Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats (1999) J. Neurosci., 19, pp. 9355-9363 Yick, L.-W., Wu, W., So, K.-F., Wong, S.Y., Time course of NOS expression and neuronal death in Clarke's nucleus following traumatic injury in adult rat spinal cord (1998) Neurosci. Lett., 241, pp. 155-158 Xu, Z., Johnson, A.K., Central renin injections: Effects on drinking and expression of immediate early genes (1998) Brain Res., 782, pp. 24-35 Xu, J., Fan, G., Chen, S., Wu, Y., Xu, X.M., Hsy, C.Y., Methylprednisolone inhibition of TNF-alpha expression and NF-κB activation after spinal cord injury in rats (1998) Mol. Brain Res., 59, pp. 135-142 Zhang, R.X., Wang, H., Ruda, M., Ladarola, M.J., Qiao, J.T., c-Fos expression in NMDA receptor-contained neurons in spinal cord in a rat model of inflammation: A double immunocytochemical study (1998) Brain Res., 795, pp. 282-286 |
| ISSN: | 00068993 |
| DOI: | 10.1016/S0006-8993(01)02717-2 |