Protective effects of progesterone administration on axonal pathology in mice with experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE), an induced model of Multiple Sclerosis presents spinal cord demyelination, axonal pathology and neuronal dysfunction. 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 cause of neurological disability. To this end, some axonal parameters were compared in EAE mice pretreated with progesterone a week before immunization with MOG(40-54) and in a group of steroid-free EAE mice. On day 16th after EAE induction, we determined in both groups and in 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 of damaged axons; c) levels of the growth associated protein GAP43 mRNA and immunopositive cell bodies, as an index of aberrant axonal sprouting. Steroid-naive EAE mice showed decreased axonal density, shrunken axons, abundance of irregular vesicular structures, degenerating APP+ axons, increased expression of GAP43 mRNA and immunoreactive protein in motoneurons. Instead, EAE mice receiving progesterone treatment showed increased axonal counts, high proportion of small diameter axons, reduced APP+ profiles, and decreased GAP43 expression. In conclusion, progesterone enhanced axonal density, decreased axonal damage and prevented GAP43 hyperexpression in the spinal cord of EAE mice. Thus, progesterone also exerts protective effects on the axonal pathology developing in EAE mice.
Garay
Laura
L
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.
Gonzalez Deniselle
Maria Claudia
MC
Meyer
Maria
M
Costa
Juan José Lopez
JJ
Lima
Analia
A
Roig
Paulina
P
De nicola
Alejandro F
AF
D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D011372:Progestins / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D019922:GAP-43 Protein; D018696:Neuroprotective Agents; D011372:Progestins; D012333:RNA, Messenger; D011374:Progesterone