INVESTIGADORES
DE NICOLA Alejandro Federico
artículos
Título:
Steroid protection in the experimental autoinmune encephalomyelitis model of multiple sclerosis
Autor/es:
GARAY L.; GONZALEZ DENISELLE, MARÍA CLAUDIA; GIERMAN L.; MEYER M.; LIMA A.; ROIG, P; DE NICOLA A.F.
Revista:
NEUROIMMUNOMODULATION.
Editorial:
Karger
Referencias:
Lugar: Suiza; Año: 2008 vol. 15 p. 76 - 83
ISSN:
1021-7401
Resumen:
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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.
