Artículo

Garay, L.; Gonzalez Deniselle, M.C.; Gierman, L.; Meyer, M.; Lima, A.; Roig, P.; De Nicola, A.F. "Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis" (2008) NeuroImmunoModulation. 15(1):76-83
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Objectives: Based on evidence that pregnant women with multiple sclerosis (MS) show a decline in the relapse rate during the third trimester and an increase during the first 3 months postpartum, the suggestion was made that high levels of circulating sex steroids are responsible for pregnancy-mediated neuroprotection. As both estradiol (E2) and progesterone exert neuroprotective and myelinating effects on the nervous system, the effects of sex steroids were studied in the experimental autoimmune encephalomyelitis (EAE) model of MS. Methods: EAE was induced in female C57BL/6 mice by administration of a myelin oligodendrocyte protein (MOG40-45) peptide. Clinical signs of EAE, myelin protein expression and neuronal parameters were determined in mice with or without hormonal treatment. Results: Progesterone given prior to EAE induction attenuated the clinical scores of the disease, slightly delayed disease onset and decreased demyelination foci, according to luxol fast blue staining (LFB), myelin basic protein (MBP) and proteolipid protein (PLP) and mRNA expression. Motoneuron expression of Na,K-ATPase mRNA was also enhanced by progesterone. In turn, combined E2 plus progesterone therapy more effectively prevented neurological deficits, fully restored LFB staining, MBP and PLP immunoreactivity and avoided inflammatory cell infiltration. On the neuronal side, steroid biotherapy increased brain-derived neurotrophic factor (BDNF) mRNA. Conclusion: Early treatment with progesterone alone or more evidently in combination with E2 showed a clinical benefit and produced myelinating and neuroprotective effects in mice with MOG 40-45-induced EAE. Therefore, sex steroids should be considered as potential novel therapeutic strategies for MS. Copyright © 2008 S. Karger AG.

Registro:

Documento: Artículo
Título:Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis
Autor:Garay, L.; Gonzalez Deniselle, M.C.; Gierman, L.; Meyer, M.; Lima, A.; Roig, P.; De Nicola, A.F.
Filiación:Laboratory of Neuroendocrine Biochemistry, Instituto de Biología Y Medicina Experimental-CONICET, Buenos Aires, Argentina
Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina
Instituto de Biología Y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:Estradiol; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Myelination; Neuroprotection; Progesterone; 1,3,5 tris(4 hydroxyphenyl) 4 propylpyrazole; adenosine triphosphatase (potassium sodium); brain derived neurotrophic factor; estradiol; estriol; ethinylestradiol; fluasterone; glucocorticoid; medroxyprogesterone; myelin basic protein; myelin oligodendrocyte glycoprotein; prasterone; progesterone; proteolipid protein; tetrahydroprogesterone; allergic encephalomyelitis; brain function; cell infiltration; cell proliferation; cellular immunity; demyelination; disease course; drug activity; drug effect; drug megadose; estrogen activity; hormonal regulation; hormone action; human; low drug dose; multiple sclerosis; myelin sheath; myelination; neuroprotection; nonhuman; pathogenesis; priority journal; protein expression; quantitative analysis; review; theoretical model; third trimester pregnancy; Animals; Brain-Derived Neurotrophic Factor; Central Nervous System; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Encephalomyelitis, Autoimmune, Experimental; Estradiol; Female; Humans; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin Basic Proteins; Myelin Proteolipid Protein; Nerve Fibers, Myelinated; Neurosecretory Systems; Progesterone; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Treatment Outcome; Up-Regulation
Año:2008
Volumen:15
Número:1
Página de inicio:76
Página de fin:83
DOI: http://dx.doi.org/10.1159/000135627
Título revista:NeuroImmunoModulation
Título revista abreviado:NeuroImmunomodulation
ISSN:10217401
CODEN:NROIE
CAS:brain derived neurotrophic factor, 218441-99-7; estradiol, 50-28-2; estriol, 50-27-1; ethinylestradiol, 57-63-6; fluasterone, 112859-71-9; medroxyprogesterone, 520-85-4; prasterone, 53-43-0; progesterone, 57-83-0; Brain-Derived Neurotrophic Factor; Estradiol, 50-28-2; Myelin Basic Proteins; Myelin Proteolipid Protein; Progesterone, 57-83-0; RNA, Messenger; Sodium-Potassium-Exchanging ATPase, EC 3.6.3.9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217401_v15_n1_p76_Garay

Referencias:

  • Elloso, M.M., Phiel, K., Henderson, R.A., Harris, H.A., Adelman, S.J., Suppression of experimental autoimmune encephalomyelitis using estrogen receptor-selective ligand (2005) J Endocrinol, 185, pp. 243-252
  • Furuzawa-Carballeda, J., Vargas-Rojas, M.I., Cabral, A.R., Autoimmune inflammation from the Th17 perspective (2007) Autoimmun Rev, 6, pp. 169-175
  • Confavreux, C., Hutchinson, M., Hours, M.M., Cortinovis-Tourniaire, P., Moreau, T., Rate of pregnancy-related relapse in multiple sclerosis (1998) N Engl J Med, 339, pp. 285-291
  • El-Etr, M., Vukusic, S., Gignoux, L., Durand-Dubief, F., Achiti, I., Baulieu, E.E., Confavreux, C., Steroid hormones in multiple sclerosis (2005) J Neurol Sci, 233, pp. 49-54
  • Hughes, M.D., Multiple sclerosis and pregnancy (2004) Neurol Clin, 22, pp. 757-769
  • Sriram, S., Steiner, I., Experimental allergic encephalomyelitis: A misleading model of multiple sclerosis (2005) Ann Neurol, 58, pp. 939-945
  • McQualter, J.L., Bernard, C.C., Multiple sclerosis: A battle between destruction and repair (2007) J Neurochem, 100, pp. 295-306
  • Sun, D., Zhang, Y., Wei, B., Peiper, S.C., Shao, H., Kaplan, H.J., Encephalitogenic activity of truncated myelin oligodendrocyte glycoprotein (MOG) peptides and their recognition by CD8+ MOG-specific T cells on oligomeric MHC class I molecules (2003) Int Immunol, 15, pp. 261-268
  • Wujek, R., Bjartmar, C., Richer, E., Ransohoff, R.M., Yu, M., Tuohy, V.K., Trapp, B.D., Axon loss in the spinal cord determines permanent neurological disability in an animal model of multiple sclerosis (2002) J Neuropathol Exp Neurol, 61, pp. 23-32
  • Zawadzka, M., Franklin, R.J., Myelin regeneration in demyelinating disorders: New developments in biology and clinical pathology (2007) Curr Opin Neurol, 20, pp. 294-298
  • McEwen, B.S., Estrogen actions throughout the brain (2002) Recent Prog Horm Res, 57, pp. 357-370
  • Garcia-Segura, L.M., Sanz, A., Mendez, P., Cross-talk between IGF-I and estradiol in the brain: Focus on neuroprotection (2006) Neuroendocrinology, 84, pp. 275-279
  • Goodman, Y., Bruce, A.J., Cheng, B., Mattson, M.P., Estrogens attenuate and CORT exacerbates excitotoxicity, oxidative injury, and amyloid-peptide toxicity in hippocampal neurons (1996) J Neurochem, 66, pp. 1836-1844
  • Ferrini, M., Lima, A., De Nicola, A.F., Estradiol abolishes autologous down regulation of glucocorticoid receptors in brain (1995) Life Sci, 57, pp. 2403-2412
  • Yune, T.Y., Kim, S.J., Lee, S.M., Lee, Y.K., Oh, Y.J., Kim, Y.C., Markelonis, G.J., Oh, T.H., Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats (2004) J Neurotrauma, 21, pp. 293-306
  • Scharfman, H.E., MacLusky, N.J., Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS (2006) Front Neuroendocrinol, 27, pp. 415-435
  • Takao, T., Flint, N., Lee, L., Ying, X., Merrill, J., Chandross, K.J., 17beta-estradiol protects oligodendrocytes from cytotoxicity induced cell death (2004) J Neurochem, 89, pp. 660-673
  • Schumacher, M., Guennoun, R., Stein, D.G., De Nicola, A.F., Progesterone: Therapeutic opportunities for neuroprotection and myelin repair (2007) Pharmacol Ther, 116, pp. 77-106
  • Gonzalez Deniselle, M.C., Garay, L., Gonzalez, S., Saravia, F., Labombarda, F., Guennoun, R., Schumacher, M., De Nicola, A.F., Progesterone modulates brain-derived neurotrophic factor and choline acetyltransferase in degenerating Wobbler motoneurons (2007) Exp Neurol, 203, pp. 406-414
  • Ghoumari, A.M., Baulieu, E.E., Schumacher, M., Progesterone increases oligodendroglial cell proliferation in rat cerebellar slice cultures (2005) Neuroscience, 135, pp. 47-58
  • Ibanez, C., Shields, S.A., El-Etr, M., Leonelli, E., Magnaghi, V., Li, W., Sim, F.J., Franklin, R.J., Steroids and the reversal of age-associated changes in myelination and remyelination (2003) Prog Neurobiol, 71, pp. 49-56
  • Labombarda, F., Gonzalez, S., Gonzalez Deniselle, M.C., Garay, L., Guennoun, R., Schumacher, M., De Nicola, A.F., Progesterone increases the expression of myelin basic protein and the number of cells showing NG2 immunostaining in the lesioned spinal cord (2006) J Neurotrauma, 23, pp. 181-192
  • Ballaré, C., Uhrig, M., Bechtold, T., Sancho, E., Di Domenico, M., Migliaccio, A., Auricchio, F., Beato, M., Two domains of the progesterone receptor interact with the estrogen receptor and are required for progesterone activation of the c-Src/Erk pathway in mammalian cells (2003) Mol Cell Biol, 23, pp. 1994-2008
  • Majewska, M.D., Harrison, N.L., Schwartz, R.D., Barker, J.L., Paul, S.M., Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor (1986) Science, 232, pp. 1004-1007
  • Druckmann, R., Druckmann, M.A., Progesterone and the immunology of pregnancy (2005) J Steroid Biochem Mol Biol, 97, pp. 389-396
  • Blois, S.M., Ilarregui, J.M., Tometten, M., Garcia, M., Orsal, A.S., Cordo-Russo, R., Toscano, M.A., Arck, P.C., A pivotal role for galectin-1 in fetomaternal tolerance (2007) Nat Med, 13, pp. 1450-1457
  • Stein, D.G., Fulop, Z.L., Progesterone and recovery after traumatic brain injury: An overview (1998) Neuroscientist, 4, pp. 435-442
  • Bansil, S., Lee, H.J., Jindal, S., Holtz, C.R., Cook, S.D., Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis (1999) Acta Neurol Scand, 99, pp. 91-94
  • Pozzilli, C., Falaschi, P., Mainero, C., Martocchia, A., D'Urso, R., Proietti, A., Frontoni, M., Filippi, M., MRI in multiple sclerosis during the menstrual cycle: Relationship with sex hormone patterns (1999) Neurology, 53, pp. 622-624
  • Keith, A.B., Effect of pregnancy on experimental allergic encephalomyelitis in guinea pigs and rats (1978) J Neurol Sci, 38, pp. 317-326
  • Evron, S., Brenner, T., Abramsky, O., Suppressive effect of pregnancy on the development of experimental allergic encephalomyelitis in rabbits (1984) Am J Reprod Immunol, 5, pp. 109-113
  • Offner, H., Neuroimmunoprotective effects of estrogen and derivatives in experimental autoimmune encephalomyelitis: Therapeutic implications for multiple sclerosis (2004) J Neurosci Res, 78, pp. 603-624
  • Mason, D., MacPhee, I., Antoni, F., The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat (1999) Immunology, 70, pp. 1-5
  • Du, C., Khalil, M.W., Sriram, S., Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice (2001) J Immunol, 167, pp. 7094-7101
  • Bebo, B.F., Fyfe-Johnson, A., Adlard, K., Beam, A.G., Vandenbark, A.A., Offner, H., Low-dose estrogen therapy ameliorates experimental autoimmune encephalomyelitis in two different inbred mouse strains (2001) J Immunol, 166, pp. 2080-2089
  • Kim, S., Liva, S.M., Dalal, M.A., Verity, M.A., Voskuhl, R.R., Estriol ameliorates autoimmune demyelinating disease: Implications for multiple sclerosis (1999) Neurology, 52, pp. 1230-1238
  • Elliot, G.A., Gibbons, A.J., Greig, M.E., A comparison of the effects of melengestrol acetate with a combination of hydrocortisone acetate and medroxyprogesterone acetate and with other steroids in the treatment of experimental allergic encephalomyelitis in Wistar rats (1973) Acta Neuropathol, 23, pp. 95-104
  • Hoffman, G.E., Le, W.W., Murphy, A.Z., Koski, C.L., Divergent effects of ovarian steroids on neuronal survival during experimental allergic encephalitis in Lewis rats (2001) Exp Neurol, 171, pp. 272-284
  • Jansson, L., Holmdahl, R., Oestrogen induced suppression of collagen arthritis. IV. Progesterone alone does not affect the course of arthritis but enhances the oestrogen-mediated therapeutic effect (1989) J Reprod Immunol, 15, pp. 141-150
  • Garay, L., Gonzalez Deniselle, M.C., Lima, A., Roig, P., De Nicola, A.F., Effects of progesterone in the mouse experimental autoimmune encephalomyelitis model of multiple sclerosis (2007) J Steroid Biochem Mol Biol, 107, pp. 228-237
  • Stahl, W.L., (Na+ + K+)-ATPase: Function, structure, and conformations (1984) Ann Neurol, 16 (SUPPL.), pp. S121-S127
  • Gonzalez, S.L., Labombarda, F., Gonzalez Deniselle, M.C., Guennoun, R., Schumacher, M., De Nicola, A.F., Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord (2004) Neuroscience, 125, pp. 605-614
  • Mitsumoto, H., Ikeda, K., Klinkosz, B., Cedarbaum, J.M., Wong, V., Lindsay, R.M., Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF (1994) Science, 265, pp. 1107-1110
  • De Nicola, A.F., Gonzalez, S.L., Labombarda, F., Deniselle, M.C., Garay, L., Guennoun, R., Schumacher, M., Progesterone treatment of spinal cord injury: Effects on receptors, neurotrophins, and myelination (2006) J Mol Neurosci, 28, pp. 3-15
  • Levine, J.M., Reynolds, R., Fawcett, J.W., The oligodendrocyte precursor cell in health and disease (2001) Trends Neurosci, 24, pp. 39-47
  • Prineas, J.W., Barnard, R.O., Kwon, E.E., Sharer, L.R., Cho, E.S., Multiple sclerosis: Remyelination of nascent lesions (1993) Ann Neurol, 33, pp. 137-151
  • Melcangi, R.V., Magnaghi, V., Martini, L., Aging in peripheral nerves: Regulation of myelin protein genes by steroid hormones (2000) Prog Neurobiol, 60, pp. 291-308

Citas:

---------- APA ----------
Garay, L., Gonzalez Deniselle, M.C., Gierman, L., Meyer, M., Lima, A., Roig, P. & De Nicola, A.F. (2008) . Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis. NeuroImmunoModulation, 15(1), 76-83.
http://dx.doi.org/10.1159/000135627
---------- CHICAGO ----------
Garay, L., Gonzalez Deniselle, M.C., Gierman, L., Meyer, M., Lima, A., Roig, P., et al. "Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis" . NeuroImmunoModulation 15, no. 1 (2008) : 76-83.
http://dx.doi.org/10.1159/000135627
---------- MLA ----------
Garay, L., Gonzalez Deniselle, M.C., Gierman, L., Meyer, M., Lima, A., Roig, P., et al. "Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis" . NeuroImmunoModulation, vol. 15, no. 1, 2008, pp. 76-83.
http://dx.doi.org/10.1159/000135627
---------- VANCOUVER ----------
Garay, L., Gonzalez Deniselle, M.C., Gierman, L., Meyer, M., Lima, A., Roig, P., et al. Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis. NeuroImmunomodulation. 2008;15(1):76-83.
http://dx.doi.org/10.1159/000135627