title: Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis.
abstract: OBJECTIVE
  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 (E(2)) 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 (MOG(40-45)) 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 E(2) 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.
  
  
  CONCLUSIONS
  Early treatment with progesterone alone or more evidently in combination with E(2) 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.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Garay
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Gonzalez Deniselle
authors.forename: Lobke
authors.initials: L
authors.lastname: Gierman
authors.forename: Maria
authors.initials: M
authors.lastname: Meyer
authors.forename: Analia
authors.initials: A
authors.lastname: Lima
authors.forename: Paulina
authors.initials: P
authors.lastname: Roig
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009490:Neurosecretory Systems / Q000276:immunology*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D000254:Sodium-Potassium-Exchanging ATPase