IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis
Autor/es:
LAURA GARAY, MARIA CLAUDIA GONZALEZ DENISELLE, LOBKE GIERMAN , MARIA MEYER , ANALIA LIMA , PAULINA ROIG AND ALEJANDRO F. DE NICOLA
Revista:
NEUROIMMUNOMODULATION.
Referencias:
Año: 2008 vol. 15 p. 76 - 83
ISSN:
1021-7401
Resumen:
Objectives: Based on evidences that pregnant women with multiple sclerosis (MS) show a decline in relapse-rate during the third trimester and an increase during the first three months post-partum, 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 in 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) protein 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 neurotrofic factor (BDNF) mRNA. Conclusion: Early treatment with progesterone alone or more evidently in combination with E2, showed clinical benefit and produced myelinating and neuroprotective effects in mice with MOG40-45 induced EAE. Therefore, sex steroids should be considered as potential novel therapeutic strategies for MS.