Pharmacotherapy with 17 beta-Estradiol and Progesterona prevents development of mouse experimental autoimmune encephalomyelitis

LAURA GARAY, MARIA C. GONZÁLEZ DENISELLE, LOBKE GIERMAN, ANALÍA LIMA, PAULINA ROIG, ALEJANDRO F. DE NICOLA

Hormone Molecular Biology and Clinical Investigation

Walter de Gruyter

Año: 2010 vol. 1

Background: Pregnant women with multiple sclerosis (MS) show disease remission in the third trimester concomitant with high circulating levels of sex steroids. Rodent experimental autoimmune encephalomyelitis (EAE) is an accepted model for MS. Previous studies have shown that monotherapy with estrogens or progesterone exert beneficial effects on EAE. The aim of the present study was to determine if estrogen and progesterone cotherapy of C57BL/6 female mice provided substantial protection from EAE. (MS) show disease remission in the third trimester concomitant with high circulating levels of sex steroids. Rodent experimental autoimmune encephalomyelitis (EAE) is an accepted model for MS. Previous studies have shown that monotherapy with estrogens or progesterone exert beneficial effects on EAE. The aim of the present study was to determine if estrogen and progesterone cotherapy of C57BL/6 female mice provided substantial protection from EAE. : Pregnant women with multiple sclerosis (MS) show disease remission in the third trimester concomitant with high circulating levels of sex steroids. Rodent experimental autoimmune encephalomyelitis (EAE) is an accepted model for MS. Previous studies have shown that monotherapy with estrogens or progesterone exert beneficial effects on EAE. The aim of the present study was to determine if estrogen and progesterone cotherapy of C57BL/6 female mice provided substantial protection from EAE. Methods: A group of mice received single pellets of progesterone (100 mg) and 17 b-estradiol (2.5 mg) subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes. subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes. progesterone (100 mg) and 17 b-estradiol (2.5 mg) subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes. subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes. : A group of mice received single pellets of progesterone (100 mg) and 17 b-estradiol (2.5 mg) subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes. subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes. b-estradiol (2.5 mg) subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes. Results: Clinical signs of EAE were substantially attenuated by estrogen and progesterone treatment. Ster- by estrogen and progesterone treatment. Ster- : Clinical signs of EAE were substantially attenuated by estrogen and progesterone treatment. Ster- oid cotherapy prevented spinal cord demyelination, infiltration of inflammatory cells and GFAPq astrogliocytes to a great extent. In motoneurons, expression of BDNF mRNA and protein was highly stimulated, indicating concomitant beneficial effects of the steroid on neuronal and glial cells. to a great extent. In motoneurons, expression of BDNF mRNA and protein was highly stimulated, indicating concomitant beneficial effects of the steroid on neuronal and glial cells. infiltration of inflammatory cells and GFAPq astrogliocytes to a great extent. In motoneurons, expression of BDNF mRNA and protein was highly stimulated, indicating concomitant beneficial effects of the steroid on neuronal and glial cells. to a great extent. In motoneurons, expression of BDNF mRNA and protein was highly stimulated, indicating concomitant beneficial effects of the steroid on neuronal and glial cells. oid cotherapy prevented spinal cord demyelination, infiltration of inflammatory cells and GFAPq astrogliocytes to a great extent. In motoneurons, expression of BDNF mRNA and protein was highly stimulated, indicating concomitant beneficial effects of the steroid on neuronal and glial cells. to a great extent. In motoneurons, expression of BDNF mRNA and protein was highly stimulated, indicating concomitant beneficial effects of the steroid on neuronal and glial cells. q astrogliocytes to a great extent. In motoneurons, expression of BDNF mRNA and protein was highly stimulated, indicating concomitant beneficial effects of the steroid on neuronal and glial cells. Conclusions: Cotherapy with estrogen and progesterone inhibits the development of major neurochemical abnormalities and clinical signs of EAE. We suggest that a combination of neuroprotective, promyelinating and immunosuppressive mechanisms are involved in these beneficial effects. inhibits the development of major neurochemical abnormalities and clinical signs of EAE. We suggest that a combination of neuroprotective, promyelinating and immunosuppressive mechanisms are involved in these beneficial effects. : Cotherapy with estrogen and progesterone inhibits the development of major neurochemical abnormalities and clinical signs of EAE. We suggest that a combination of neuroprotective, promyelinating and immunosuppressive mechanisms are involved in these beneficial effects.