Pharmacotherapy with 17 beta-Estradiol and Progesterone prevents development of mouse Experimental Autoimmune Encephalomyelitis

GARAY L; GONZALEZ DENISELLE MC; GIERMAN L; LIMA A; ROIG P; DE NICOLA AF

Hormone Molecular Biology and Clinical Investigation

De Gruyter

Año: 2010 p. 43 - 51

1868-1891

Background: Pregnant women with multiple sclerosis(MS) show disease remission in the third trimesterconcomitant with high circulating levels of sex steroids.Rodent experimental autoimmune encephalomyelitis(EAE) is an accepted model for MS. Previousstudies have shown that monotherapy with estrogensor progesterone exert beneficial effects on EAE. Theaim of the present study was to determine if estrogenand progesterone cotherapy of C57BL/6 female miceprovided substantial protection from EAE.Methods: A group of mice received single pellets ofprogesterone (100 mg) and 17 b-estradiol (2.5 mg)subcutaneously 1 week before EAE induction, whereasanother group were untreated before EAE induction.On day 16 we compared the two EAE groups andcontrol mice in terms of clinical scores, spinal corddemyelination, expression of myelin basic proteinand proteolipid protein, macrophage cell infiltration,neuronal expression of brain-derived neurotrophicfactor mRNA and protein, and the number of glialfribrillary acidic protein (GFAP)-immunopositiveastrocytes.Results: Clinical signs of EAE were substantially attenuatedby estrogen and progesterone treatment. Steroid cotherapy prevented spinal cord demyelination,infiltration of inflammatory cells and GFAPq astrogliocytesto a great extent. In motoneurons, expressionof BDNF mRNA and protein was highly stimulated,indicating concomitant beneficial effects of the steroidon neuronal and glial cells.Conclusions: Cotherapy with estrogen and progesteroneinhibits the development of major neurochemicalabnormalities and clinical signs of EAE. We suggestthat a combination of neuroprotective, promyelinatingand immunosuppressive mechanisms are involvedin these beneficial effects.