Protective effects of Progesterone administration on axonal pathology in mice with Experimental Autoimmune Encephalomyelitis

GARAY L; GONZALEZ DENISELLE MC; MEYER M; LOPEZ COSTA, J.J; LIMA A; ROIG P; DE NICOLA A. F.

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 2009 vol. 4 p. 177 - 182

0006-8993

Experimental autoimmune encephalomyelitis (EAE), an induced model of MultipleSclerosis presents spinal cord demyelination, axonal pathology and neuronaldysfunction. Previous work has shown that progesterone attenuated the clinical severity,demyelination and neuronal dysfunction of EAE mice (Garay et al., J. Steroid Biochem. Mol.Biol., 2008). Here we studied if progesterone also prevented axonal damage, a main causeof neurological disability. To this end, some axonal parameters were compared in EAE micepretreated with progesterone a week before immunization with MOG40–54 and in a group ofsteroid-free EAE mice. On day 16th after EAE induction, we determined in both groups andin control mice: a) axonal density in semithin sections of the spinal cord ventral funiculus;b) appearance of amyloid precursor protein (APP) immunopositive spheroids as an index ofdamaged axons; c) levels of the growth associated protein GAP43 mRNA andimmunopositive cell bodies, as an index of aberrant axonal sprouting. Steroid-naive EAEmice showed decreased axonal density, shrunken axons, abundance of irregular vesicularstructures, degenerating APP+ axons, increased expression of GAP43 mRNA andimmunoreactive protein in motoneurons. Instead, EAE mice receiving progesteronetreatment showed increased axonal counts, high proportion of small diameter axons,reduced APP+ profiles, and decreased GAP43 expression. In conclusion, progesteroneenhanced axonal density, decreased axonal damage and prevented GAP43 hyperexpressionin the spinal cord of EAE mice. Thus, progesterone also exerts protective effects on theaxonal pathology developing in EAE mice.