IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Progesterone attenuates axonal pathology in the spinal cord of mice with experimental autoimmune encephalomyelitis
Autor/es:
LAURA GARAY, MARIA C. GONZÁLEZ DENISELLE, MARÍA MEYER, JUAN JOSÉ LÓPEZ COSTA, ANALÍA LIMA, PAULINA ROIG, ALEJANDRO F. DE NICOLA
Revista:
BRAIN RESEARCH
Editorial:
ELSEVIER
Referencias:
Año: 2009 vol. 1283 p. 177 - 185
ISSN:
0006-8993
Resumen:
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 MOG4054 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
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
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
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
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
4054 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